Summary: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.

Top Publications

  1. ncbi Wound healing--aiming for perfect skin regeneration
    P Martin
    Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK
    Science 276:75-81. 1997
  2. pmc Defining the epithelial stem cell niche in skin
    Tudorita Tumbar
    Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, Rockefeller University, New York, NY 10021, USA
    Science 303:359-63. 2004
  3. ncbi beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin
    J Huelsken
    Max Delbrueck Center for Molecular Medicine, Robert Roessle Strasse 10, 13092, Berlin, Germany
    Cell 105:533-45. 2001
  4. ncbi Cellular motility driven by assembly and disassembly of actin filaments
    Thomas D Pollard
    Department of Cellular, Molecular, and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Cell 112:453-65. 2003
  5. ncbi A skin microRNA promotes differentiation by repressing 'stemness'
    Rui Yi
    Howard Hughes Medical Institute, The Rockefeller University, New York City, New York 10065, USA
    Nature 452:225-9. 2008
  6. ncbi Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis
    Leslie van der Fits
    Department of Dermatology, Erasmus Medical Center, Rotterdam, The Netherlands
    J Immunol 182:5836-45. 2009
  7. ncbi IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis
    Kerstin Wolk
    Interdisciplinary Group of Molecular Immunopathology, Dermatology Medical Immunology, University Hospital Charite, Berlin, Germany
    Eur J Immunol 36:1309-23. 2006
  8. ncbi Unique and redundant functions of integrins in the epidermis
    Coert Margadant
    Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    FASEB J 24:4133-52. 2010
  9. pmc p63 identifies keratinocyte stem cells
    G Pellegrini
    Laboratory of Tissue Engineering IDI, Istituto Dermopatico dell Immacolata, 00040 Rome, Italy
    Proc Natl Acad Sci U S A 98:3156-61. 2001
  10. pmc p63 is the molecular switch for initiation of an epithelial stratification program
    Maranke I Koster
    Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Genes Dev 18:126-31. 2004

Detail Information

Publications385 found, 100 shown here

  1. ncbi Wound healing--aiming for perfect skin regeneration
    P Martin
    Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK
    Science 276:75-81. 1997
  2. pmc Defining the epithelial stem cell niche in skin
    Tudorita Tumbar
    Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, Rockefeller University, New York, NY 10021, USA
    Science 303:359-63. 2004
    ..Many of the >100 messenger RNAs preferentially expressed in the niche encode surface receptors and secreted proteins, enabling LRCs to signal and respond to their environment...
  3. ncbi beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin
    J Huelsken
    Max Delbrueck Center for Molecular Medicine, Robert Roessle Strasse 10, 13092, Berlin, Germany
    Cell 105:533-45. 2001
    ..Further analysis demonstrates that beta-catenin is essential for fate decisions of skin stem cells: in the absence of beta-catenin, stem cells fail to differentiate into follicular keratinocytes, but instead adopt an epidermal fate.
  4. ncbi Cellular motility driven by assembly and disassembly of actin filaments
    Thomas D Pollard
    Department of Cellular, Molecular, and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Cell 112:453-65. 2003
    ..Profilin catalyzes the exchange of ADP for ATP, refilling the pool of ATP-actin monomers bound to profilin, ready for elongation...
  5. ncbi A skin microRNA promotes differentiation by repressing 'stemness'
    Rui Yi
    Howard Hughes Medical Institute, The Rockefeller University, New York City, New York 10065, USA
    Nature 452:225-9. 2008
    ..Our findings suggest that miR-203 defines a molecular boundary between proliferative basal progenitors and terminally differentiating suprabasal cells, ensuring proper identity of neighbouring layers...
  6. ncbi Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis
    Leslie van der Fits
    Department of Dermatology, Erasmus Medical Center, Rotterdam, The Netherlands
    J Immunol 182:5836-45. 2009
    ..This rapid and convenient model allows further elucidation of pathogenic mechanisms and evaluation of new therapies in psoriasis...
  7. ncbi IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis
    Kerstin Wolk
    Interdisciplinary Group of Molecular Immunopathology, Dermatology Medical Immunology, University Hospital Charite, Berlin, Germany
    Eur J Immunol 36:1309-23. 2006
    ..demonstrate that IL-22, in contrast to its relative IFN-gamma, regulates the expression of only a few genes in keratinocytes. This is due to varied signal transduction...
  8. ncbi Unique and redundant functions of integrins in the epidermis
    Coert Margadant
    Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    FASEB J 24:4133-52. 2010
    ..Furthermore, we discuss human pathologies associated with altered integrin functions in the epidermis...
  9. pmc p63 identifies keratinocyte stem cells
    G Pellegrini
    Laboratory of Tissue Engineering IDI, Istituto Dermopatico dell Immacolata, 00040 Rome, Italy
    Proc Natl Acad Sci U S A 98:3156-61. 2001
    The proliferative compartment of stratified squamous epithelia consists of stem and transient amplifying (TA) keratinocytes. Some polypeptides are more abundant in putative epidermal stem cells than in TA cells, but no polypeptide ..
  10. pmc p63 is the molecular switch for initiation of an epithelial stratification program
    Maranke I Koster
    Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Genes Dev 18:126-31. 2004
    ..Our data demonstrate that p63 plays a dual role: initiating epithelial stratification during development and maintaining proliferative potential of basal keratinocytes in mature epidermis.
  11. pmc Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice
    Mikio Furuse
    Department of Cell Biology, Kyoto University Faculty of Medicine, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    J Cell Biol 156:1099-111. 2002
    ..revealed that in these mice the epidermal barrier was severely affected, although the layered organization of keratinocytes appeared to be normal...
  12. ncbi De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin
    U Gat
    Howard Hughes Medical Institute, The University of Chicago, Illinois 60637, USA
    Cell 95:605-14. 1998
    ..We report that this pathway operates in keratinocytes and that mice expressing a stabilized beta-catenin controlled by an epidermal promoter undergo a process ..
  13. ncbi Capturing and profiling adult hair follicle stem cells
    Rebecca J Morris
    Department of Dermatology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Nat Biotechnol 22:411-7. 2004
    ..Ultimately, these findings provide potential targets for the treatment of hair loss and other disorders of skin and hair...
  14. ncbi Endogenous antimicrobial peptides and skin infections in atopic dermatitis
    Peck Y Ong
    Division of Allergy and Immunology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA
    N Engl J Med 347:1151-60. 2002
    ..We compared the levels of expression of LL-37 and human beta-defensin 2 (HBD-2) in inflamed skin from patients with atopic dermatitis and from those with psoriasis...
  15. pmc p63 regulates proliferation and differentiation of developmentally mature keratinocytes
    Amy B Truong
    VA Palo Alto Health Care System, Palo Alto, California 94304, USA
    Genes Dev 20:3185-97. 2006
    ..These data indicate that p63 is required for both the proliferative and differentiation potential of developmentally mature keratinocytes.
  16. pmc Genome-wide profiling of p63 DNA-binding sites identifies an element that regulates gene expression during limb development in the 7q21 SHFM1 locus
    Evelyn N Kouwenhoven
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    PLoS Genet 6:e1001065. 2010
    ..profiling by chromatin immunoprecipitation (ChIP), followed by deep sequencing (ChIP-seq) in primary human keratinocytes, and identified potential target genes and regulatory elements controlled by p63...
  17. ncbi TLR3 deficiency in patients with herpes simplex encephalitis
    Shen Ying Zhang
    Human Genetics of Infectious Diseases, Institut National de la Sante et de la Recherche Medicale INSERM, U550, Faculty Necker, Paris 75015, France
    Science 317:1522-7. 2007
    ..Human TLR3 appears to be redundant in host defense to most microbes but is vital for natural immunity to HSV-1 in the CNS, which suggests that neurotropic viruses have contributed to the evolutionary maintenance of TLR3...
  18. pmc The magical touch: genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin
    V Vasioukhin
    Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 96:8551-6. 1999
    ..embryos recombine genetically introduced loxP sequences efficiently and selectively in the genomes of keratinocytes that reside in embryonic day 14.5 skin, tongue, and esophagus...
  19. pmc Asymmetric cell divisions promote Notch-dependent epidermal differentiation
    Scott E Williams
    Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, New York 10065, USA
    Nature 470:353-8. 2011
  20. ncbi Isolation and short-term culture of primary keratinocytes, hair follicle populations and dermal cells from newborn mice and keratinocytes from adult mice for in vitro analysis and for grafting to immunodeficient mice
    Ulrike Lichti
    NIH NCI CCR, Laboratory of Cancer Biology and Genetics, In vitro Pathogenesis Section, 37 Convent Drive, Building 37 4068, Bethesda, Maryland 20892 4255, USA
    Nat Protoc 3:799-810. 2008
    Protocols for preparing and culturing primary keratinocytes from newborn and adult mouse epidermis have evolved over the past 35 years...
  21. ncbi Keratinocyte-fibroblast interactions in wound healing
    Sabine Werner
    Institute of Cell Biology, Eidgenossische Technische Hochschule Zurich, Honggerberg, Zurich, Switzerland
    J Invest Dermatol 127:998-1008. 2007
    ..There is ample evidence that keratinocytes stimulate fibroblasts to synthesize growth factors, which in turn will stimulate keratinocyte proliferation in ..
  22. pmc RhoA is dispensable for skin development, but crucial for contraction and directed migration of keratinocytes
    Ben Jackson
    Biomedical Institute, BRIC, University of Copenhagen, 2200 Copenhagen, Denmark
    Mol Biol Cell 22:593-605. 2011
    ..Primary RhoA-null keratinocytes, however, displayed an increased percentage of multinucleated cells, defective maturation of cell-cell ..
  23. ncbi Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis
    Andrea Chiricozzi
    Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA
    J Invest Dermatol 131:677-87. 2011
    ..Our data predict that psoriasis therapy with either TNF or IL-17 antagonists will produce greater modulation of the synergistic/additive gene set, which consists of the most highly expressed genes in psoriasis skin lesions...
  24. ncbi Dickkopf 1 (DKK1) regulates skin pigmentation and thickness by affecting Wnt/beta-catenin signaling in keratinocytes
    Yuji Yamaguchi
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    FASEB J 22:1009-20. 2008
    The epidermis (containing primarily keratinocytes and melanocytes) overlies the dermis (containing primarily fibroblasts) of human skin...
  25. pmc Acetylation of Rb by PCAF is required for nuclear localization and keratinocyte differentiation
    Adam Pickard
    Centre for Cancer Research and Cell Biology, Queen s University Belfast, Belfast, BT9 7BL, UK
    J Cell Sci 123:3718-26. 2010
    ..Studies indicate that acetylation is a mechanism for controlling Rb localization in human keratinocytes, with either reduction of the PCAF or exogenous expression of the deacetylase SIRT1, resulting in ..
  26. ncbi Epidermal growth factor receptor-dependent, NF-kappaB-independent activation of the phosphatidylinositol 3-kinase/Akt pathway inhibits ultraviolet irradiation-induced caspases-3, -8, and -9 in human keratinocytes
    Hui Qin Wang
    Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0609, USA
    J Biol Chem 278:45737-45. 2003
    ..Human skin cells (keratinocytes) are commonly exposed to UV irradiation from the sun...
  27. pmc AMP-activated protein kinase contributes to UV- and H2O2-induced apoptosis in human skin keratinocytes
    Cong Cao
    Department of Biology, Providence College, Providence, Rhode Island 02918 0001, USA
    J Biol Chem 283:28897-908. 2008
    ..the first time that UV and H(2)O(2) induce AMPK activation (Thr(172) phosphorylation) in cultured human skin keratinocytes. UV and H(2)O(2) also phosphorylate LKB1, an upstream signal of AMPK, in an epidermal growth factor receptor-..
  28. ncbi Mechanisms of IFN-γ-induced apoptosis of human skin keratinocytes in patients with atopic dermatitis
    Ana Rebane
    Swiss Institute of Allergy and Asthma Research SIAF, University of Zurich, Davos, Switzerland
    J Allergy Clin Immunol 129:1297-306. 2012
    Enhanced apoptosis of keratinocytes is the main cause of eczema and spongiosis in patients with the common inflammatory skin disease atopic dermatitis (AD).
  29. pmc A role for caveolin-1 in desmoglein binding and desmosome dynamics
    D Brennan
    Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Oncogene 31:1636-48. 2012
  30. pmc Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells
    Matthew LeBoeuf
    Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
    Dev Cell 19:807-18. 2010
    ..are ectopically expressed, and HDACs bind and are active at their promoter regions in normal undifferentiated keratinocytes. Mutant embryos display increased levels of acetylated p53, which opposes p63 functions, and p53 is required ..
  31. ncbi p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest
    G J Hannon
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724
    Nature 371:257-61. 1994
    ..p15 expression is induced approximately 30-fold in human keratinocytes by treatment with TGF-beta, suggesting that p15 may act as an effector of TGF-beta-mediated cell cycle arrest...
  32. pmc Desmosome disassembly in response to pemphigus vulgaris IgG occurs in distinct phases and can be reversed by expression of exogenous Dsg3
    Jean M Jennings
    Departments of Cell Biology and Dermatology, Emory University, Atlanta, Georgia, USA
    J Invest Dermatol 131:706-18. 2011
    ..The mechanism by which PV IgG disrupts adhesion is not fully understood. To address this issue, primary human keratinocytes (KCs) and patient IgG were used to define the morphological, biochemical, and functional changes triggered by ..
  33. ncbi Inflammation in wound repair: molecular and cellular mechanisms
    Sabine A Eming
    Department of Dermatology, University of Cologne, Cologne, Germany
    J Invest Dermatol 127:514-25. 2007
    ..In this paper, we review cellular and molecular mechanisms controlling inflammation in cutaneous tissue repair and provide a rationale for targeting the inflammatory phase in order to modulate the outcome of the healing response...
  34. pmc Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin
    B J Merrill
    Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637, USA
    Genes Dev 15:1688-705. 2001
    In skin, multipotent stem cells generate the keratinocytes of the epidermis, sebaceous gland, and hair follicles. In this paper, we show that Tcf3 and Lef1 control these differentiation lineages...
  35. ncbi Notch1 functions as a tumor suppressor in mouse skin
    Michael Nicolas
    Ludwig Institute for Cancer Research, Lausanne Branch, University Lausanne, 1066 Epalinges, Switzerland
    Nat Genet 33:416-21. 2003
    ..Notch1 deficiency in skin and in primary keratinocytes results in increased and sustained expression of Gli2, causing the development of basal-cell carcinoma-like ..
  36. pmc Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways
    K E Nograles
    Laboratory of Investigative Dermatology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Br J Dermatol 159:1092-102. 2008
    ..Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines, yet the relative contribution of interferon (IFN)-gamma, interleukin (IL)-17 and IL-22 on disease pathogenesis is still unknown...
  37. pmc CpG methylation of half-CRE sequences creates C/EBPalpha binding sites that activate some tissue-specific genes
    Vikas Rishi
    Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Building 37, Room 3128, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 107:20311-6. 2010
    ..These data identify a new function for methyl CpGs: producing DNA binding sites at half-CRE and half-C/EBP sequences for C/EBPα that are needed to activate tissue-specific genes...
  38. ncbi Enrichment for living murine keratinocytes from the hair follicle bulge with the cell surface marker CD34
    Carol S Trempus
    Cancer Biology Group, National Center for Toxicogenomics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    J Invest Dermatol 120:501-11. 2003
    ..the hematopoietic stem and progenitor cell marker, CD34, as a potential marker of hair follicle bulge keratinocytes. Using a CD34-specific antibody, we identified intense membrane staining on keratinocytes in the bulge region ..
  39. ncbi IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes
    Katia Boniface
    Laboratoire Cytokines et Inflammation, UPRES EA 3806, Pole Biologie Sante, Universite de Poitiers, Poitiers, France
    J Immunol 174:3695-702. 2005
    ..In the present study, we show that short-term cultured human epidermal keratinocytes express a functional IL-22R but no IL-10R...
  40. ncbi Perp is a p63-regulated gene essential for epithelial integrity
    Rebecca A Ihrie
    Division of Radiation and Cancer Biology, Stanford University School of Medicine, Stanford, California 94305, USA
    Cell 120:843-56. 2005
    ..These findings demonstrate that Perp is a key effector in the p63 developmental program, playing an essential role in an adhesion subprogram central to epithelial integrity and homeostasis...
  41. pmc From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma
    Vladimir Ratushny
    Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    J Clin Invest 122:464-72. 2012
    ..Insights gained from modeling cSCCs have suggested innovative therapeutic targets for treating these lesions...
  42. pmc Interferon-β induces cellular senescence in cutaneous human papilloma virus-transformed human keratinocytes by affecting p53 transactivating activity
    Maria V Chiantore
    Department of Infectious, Parasitic and Immune Mediated Diseases, Istituto Superiore di Sanita, Rome, Italy
    PLoS ONE 7:e36909. 2012
    Interferon (IFN)-β inhibits cell proliferation and affects cell cycle in keratinocytes transformed by both mucosal high risk Human Papilloma Virus (HPV) and cutaneous HPV E6 and E7 proteins...
  43. pmc p63-microRNA feedback in keratinocyte senescence
    Pia Rivetti di Val Cervo
    Istituto Dermopatico dell Immacolata Istituto di Ricovero e Cura a Carattere Scientifico, Laboratory of Biochemistry, Department of Experimental Medicine and Biochemical Sciences, and University of Rome Tor Vergata, 00133 Rome, Italy
    Proc Natl Acad Sci U S A 109:1133-8. 2012
    We investigated the expression of microRNAs (miRNAs) associated with replicative senescence in human primary keratinocytes. A cohort of miRNAs up-regulated in senescence was identified by genome-wide miRNA profiling, and their change in ..
  44. pmc ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation
    George L Sen
    Department of Medicine Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USA
    Dev Cell 22:669-77. 2012
    ..ZNF750 thus directly links a tissue-specifying factor, p63, to an effector of terminal differentiation, KLF4, and represents a potential future target for disorders of this process...
  45. ncbi Notch activation by the metalloproteinase ADAM17 regulates myeloproliferation and atopic barrier immunity by suppressing epithelial cytokine synthesis
    Aditya Murthy
    Ontario Cancer Institute, Toronto, Canada
    Immunity 36:105-19. 2012
    Epithelial cells of mucosal tissues provide a barrier against environmental stress, and keratinocytes are key decision makers for immune cell function in the skin...
  46. pmc Noncentrosomal microtubules and type II myosins potentiate epidermal cell adhesion and barrier formation
    Kaelyn D Sumigray
    Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA
    J Cell Biol 199:513-25. 2012
    ..We propose that noncentrosomal microtubules act through myosin II recruitment to potentiate cell adhesion in the differentiating epidermis, thus forming a robust mechanical and chemical barrier against the external environment...
  47. ncbi Role of melanoma chondroitin sulphate proteoglycan in patterning stem cells in human interfollicular epidermis
    James Legg
    Keratinocyte Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London, WC2A 3PX, UK
    Development 130:6049-63. 2003
    ..Stem cells can be distinguished from other keratinocytes by high expression of beta1 integrins and lack of expression of terminal differentiation markers; they divide ..
  48. ncbi Hydroxyl radical mediates cisplatin-induced apoptosis in human hair follicle dermal papilla cells and keratinocytes through Bcl-2-dependent mechanism
    Sudjit Luanpitpong
    Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
    Apoptosis 16:769-82. 2011 investigated the apoptotic effect of cisplatin in human hair follicle dermal papilla cells and HaCaT keratinocytes, and determined the identity and role of specific reactive oxygen species (ROS) involved in the process...
  49. pmc Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis
    William R Swindell
    Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 6:e18266. 2011
  50. pmc Assessment of the psoriatic transcriptome in a large sample: additional regulated genes and comparisons with in vitro models
    Johann E Gudjonsson
    Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Invest Dermatol 130:1829-40. 2010
    ..Comparison of the psoriatic transcriptome to the transcriptomes of cytokine-stimulated cultured keratinocytes (IL-17, IL-22, IL-1alpha, IFN-gamma, TNF-alpha, and OSM) showed surprisingly little overlap, with the cytokine-..
  51. pmc p63 control of desmosome gene expression and adhesion is compromised in AEC syndrome
    Giustina Ferone
    Fondazione IRCCS SDN, Napoli, Italy
    Hum Mol Genet 22:531-43. 2013
    ..Expression of desmosomal cadherins and desmoplakin was strongly reduced in AEC mutant keratinocytes and in newborn epidermis...
  52. pmc Evidence for alteration of EZH2, BMI1, and KDM6A and epigenetic reprogramming in human papillomavirus type 16 E6/E7-expressing keratinocytes
    Paula L Hyland
    Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
    J Virol 85:10999-1006. 2011
    ..We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and ..
  53. pmc Ultraviolet irradiation-induces epidermal growth factor receptor (EGFR) nuclear translocation in human keratinocytes
    Yiru Xu
    Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Cell Biochem 107:873-80. 2009
    ..role in mediating ultraviolet (UV) irradiation-induced signal transduction and gene expression in human keratinocytes. EGFR activation results from increased phosphorylation on specific tyrosine residues in the C-terminal ..
  54. pmc Global gene expression analysis reveals evidence for decreased lipid biosynthesis and increased innate immunity in uninvolved psoriatic skin
    Johann E Gudjonsson
    Department of Dermatology, University of Michigan, 1910 Taubman Center, Ann Arbor, Michigan 48109, USA
    J Invest Dermatol 129:2795-804. 2009
    ..Taken together, our results identify a "pre-psoriatic" gene expression signature, suggesting decreased lipid biosynthesis and increased innate immunity in uninvolved psoriatic skin...
  55. pmc Dual role of COUP-TF-interacting protein 2 in epidermal homeostasis and permeability barrier formation
    Olga Golonzhka
    Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, USA
    J Invest Dermatol 129:1459-70. 2009
    ..The analysis of conditionally null mice, in which expression of CTIP2 was ablated specifically in epidermal keratinocytes, suggests that CTIP2 functions in both cell and non-cell autonomous contexts to exert regulatory influence ..
  56. ncbi Extracellular matrix and keratinocyte migration
    E A O'Toole
    Centre for Cutaneous Research, St Bartholomew s and the Royal London School of Medicine and Dentistry, London, UK
    Clin Exp Dermatol 26:525-30. 2001
  57. pmc Human keratinocytes are efficiently immortalized by a Rho kinase inhibitor
    Sandra Chapman
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA
    J Clin Invest 120:2619-26. 2010
    Primary human keratinocytes are useful for studying the pathogenesis of many different diseases of the cutaneous and mucosal epithelia...
  58. pmc Targeted disruption of the LAMA3 gene in mice reveals abnormalities in survival and late stage differentiation of epithelial cells
    M C Ryan
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    J Cell Biol 145:1309-23. 1999
    ..we were able to detect a new ligand for integrin alpha3beta1 in the epidermal BM, suggesting that basal keratinocytes can utilize integrin alpha3beta1 to interact with an alternative ligand...
  59. pmc Synthesis of infectious human papillomavirus type 18 in differentiating epithelium transfected with viral DNA
    C Meyers
    Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey 17033, USA
    J Virol 71:7381-6. 1997
    ..We have artificially introduced linearized HPV18 genomic DNA into primary keratinocytes by electroporation, followed by clonal expansion and induction of epithelial stratification and ..
  60. pmc Herpes simplex virus type 1 enters human epidermal keratinocytes, but not neurons, via a pH-dependent endocytic pathway
    Anthony V Nicola
    Medical Virology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 1888, USA
    J Virol 79:7609-16. 2005
    ..of lysosomotropic agents, which raise endosomal pH, blocked HSV entry into primary and transformed human keratinocytes, but not into human neurons or neuroblastoma lines...
  61. pmc TAp63 prevents premature aging by promoting adult stem cell maintenance
    Xiaohua Su
    Department of Molecular and Cellular Oncology, Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Cell Stem Cell 5:64-75. 2009
    ..These data indicate that TAp63 serves to maintain adult skin stem cells by regulating cellular senescence and genomic stability, thereby preventing premature tissue aging...
  62. pmc Modulation of TLR2 protein expression by miR-105 in human oral keratinocytes
    Manjunatha R Benakanakere
    Center for Oral Health and Systemic Disease, University of Louisville School of Dentistry, Louisville, Kentucky 40202, USA
    J Biol Chem 284:23107-15. 2009
    ..Our model system comprised primary human keratinocytes, which exhibited robust differences in inflammatory cytokine production (interleukin-6 and tumor necrosis ..
  63. pmc MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis
    L M Coussens
    Cancer Research Institute, University of California, San Francisco 94143, USA
    Cell 103:481-90. 2000
    ..Thus, inflammatory cells can be coconspirators in carcinogenesis...
  64. pmc Microbial symbiosis with the innate immune defense system of the skin
    Richard L Gallo
    Department of Medicine, Division of Dermatology, University of California, San Diego, San Diego, California 92121, USA
    J Invest Dermatol 131:1974-80. 2011
    ..Our resident commensal microbes produce their own AMPs, act to enhance the normal production of AMPs by keratinocytes, and are beneficial to maintaining inflammatory homeostasis by suppressing excess cytokine release after minor ..
  65. pmc Control of differentiation in a self-renewing mammalian tissue by the histone demethylase JMJD3
    George L Sen
    VA Palo Alto Health Care System, Palo Alto, California 94305, USA
    Genes Dev 22:1865-70. 2008
    ..Within epidermal tissue, JMJD3 depletion blocked differentiation, while active JMJD3 dominantly induced it. These results indicate that epigenetic derepression by JMJD3 controls mammalian epidermal differentiation...
  66. pmc Pemphigus vulgaris IgG-induced desmoglein-3 endocytosis and desmosomal disassembly are mediated by a clathrin- and dynamin-independent mechanism
    Emmanuella Delva
    Graduate Program in Biochemistry, Cell, and Developmental Biology, Department of Cell Biology, Emory University, Atlanta, GA 30332, USA
    J Biol Chem 283:18303-13. 2008
    ..To define the endocytic machinery involved in PV IgG-induced Dsg3 internalization, human keratinocytes were incubated with PV IgG, and various tools were used to perturb distinct endocytic pathways. The PV IgG...
  67. ncbi Actin and serum response factor transduce physical cues from the microenvironment to regulate epidermal stem cell fate decisions
    John T Connelly
    Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, UK
    Nat Cell Biol 12:711-8. 2010
    ..On small (20 microm diameter) circular islands, keratinocytes remained rounded, and differentiated at higher frequency than cells that could spread on large (50 microm ..
  68. pmc A regulatory feedback loop involving p63 and IRF6 links the pathogenesis of 2 genetically different human ectodermal dysplasias
    Francesca Moretti
    Department of Dermatology, University of Rome Tor Vergata, Rome, Italy
    J Clin Invest 120:1570-7. 2010
    ..Here, we used human and mouse primary keratinocytes and mouse models to investigate the role of p63 and IRF6 in proliferation and differentiation...
  69. pmc Cytokine modulation of atopic dermatitis filaggrin skin expression
    Michael D Howell
    Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Allergy Clin Immunol 120:150-5. 2007
    ..Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by a defective skin barrier function. Recent studies have reported mutations of the skin barrier gene encoding filaggrin in a subset of patients with AD...
  70. ncbi IL-22 increases the innate immunity of tissues
    Kerstin Wolk
    Corporate Research Business Area Dermatology, Schering AG, D 13342 Berlin, Germany
    Immunity 21:241-54. 2004
    ..The expression of IL-22 receptor in keratinocytes was upregulated by Interferon-gamma...
  71. pmc HPV16 E7 protein and hTERT proteins defective for telomere maintenance cooperate to immortalize human keratinocytes
    Jonathan Miller
    Department of Pathology, Georgetown University Medical Center, Washington, D C, United States of America
    PLoS Pathog 9:e1003284. 2013
    ..type 16 (HPV-16) E6 protein, which cooperates with the viral E7 protein in the immortalization of primary keratinocytes. In the current study, we made the surprising finding that catalytically inactive hTERT (hTERT-D868A), ..
  72. pmc Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence
    Kim B Jensen
    Keratinocyte Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Proc Natl Acad Sci U S A 103:11958-63. 2006
    ..Lrig1 acted in part by negatively regulating the Myc promoter. We propose that Lrig1 maintains epidermal stem cells in a quiescent nondividing state, and that Lrig1 down-regulation triggers proliferation...
  73. ncbi Role of aPKC isoforms and their binding partners Par3 and Par6 in epidermal barrier formation
    Iris Helfrich
    Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
    J Invest Dermatol 127:782-91. 2007
    ..of the polarity protein atypical PKC (aPKC) and its binding partners Par3 and Par6 in epidermis and primary keratinocytes of mice...
  74. ncbi IL-17 amplifies human contact hypersensitivity by licensing hapten nonspecific Th1 cells to kill autologous keratinocytes
    Davide Pennino
    Laboratory of Experimental Immunology, Istituto Dermopatico dell Immacolata Istituto di Ricovero e Cura a Carattere Scientifico, Via dei Monti di Creta 104, 00167 Rome, Italy
    J Immunol 184:4880-8. 2010
    ..In the IFN-gamma-dominated ACD environment, IL-17-releasing T cells affect immune function of keratinocytes by promoting CXCL8, IL-6, and HBD-2 production...
  75. ncbi Distinct strains of Propionibacterium acnes induce selective human beta-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors
    Istvan Nagy
    Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary
    J Invest Dermatol 124:931-8. 2005
    ..acnes) in the pilosebaceous unit. We investigated whether direct interaction of P. acnes with keratinocytes might be involved in the inflammation and ductal hypercornification in acne. The capacities of different P...
  76. ncbi Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate
    P Zhou
    Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637, USA
    Genes Dev 9:700-13. 1995
    ..two factors only LEF-1 is expressed in hair follicles; it can be cloned in both splice forms from human skin keratinocytes and it can bind to these sites in the hair promoters...
  77. pmc Effects of cerium oxide nanoparticles on the growth of keratinocytes, fibroblasts and vascular endothelial cells in cutaneous wound healing
    Srinivasulu Chigurupati
    Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA
    Biomaterials 34:2194-201. 2013
    Rapid and effective wound healing requires a coordinated cellular response involving fibroblasts, keratinocytes and vascular endothelial cells (VECs)...
  78. pmc Cyclin D1 downregulation is important for permanent cell cycle exit and initiation of differentiation induced by anchorage-deprivation in human keratinocytes
    Kayoko Nishi
    Department of Environmental Toxicology, School of Agricultural Sciences, University of California Davis, Davis, California 95616, USA
    J Cell Biochem 106:63-72. 2009
    ..Cyclin D1 overexpression antagonized Keratin 10 expression in suspended HaCaT cells. The result demonstrates the importance of cyclin D1 down regulation for proper initiation of keratinocyte differentiation...
  79. pmc Upregulation of FOXM1 induces genomic instability in human epidermal keratinocytes
    Muy Teck Teh
    Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Turner Street, London E1 2AD, UK
    Mol Cancer 9:45. 2010
    ..This indicates that upregulation of FOXM1 may be an early molecular signal required for aberrant cell cycle and cancer initiation...
  80. pmc Polycomb group proteins are key regulators of keratinocyte function
    Richard L Eckert
    Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    J Invest Dermatol 131:295-301. 2011
    ..These proteins are expressed in progenitor cells, in the basal layer, and in suprabasal keratinocytes, and the level, timing, and distribution of expression suggest that the PcG proteins have a central role in ..
  81. pmc Jarid2 regulates mouse epidermal stem cell activation and differentiation
    Stefania Mejetta
    Department of Differentiation and Cancer, Center for Genomic Regulation and UPF, Barcelona, Spain
    EMBO J 30:3635-46. 2011
    ..We conclude that Jarid2 is required for the scheduled proliferation of epidermal stem and progenitor cells necessary to maintain epidermal homeostasis...
  82. pmc p38 MAPK activation is downstream of the loss of intercellular adhesion in pemphigus vulgaris
    Xuming Mao
    Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 286:1283-91. 2011
    ..PV mAbs that cause endocytosis of Dsg3 but do not dissociate keratinocytes because of compensatory adhesion by Dsg1 do not activate p38...
  83. pmc Kindlin-1 Is required for RhoGTPase-mediated lamellipodia formation in keratinocytes
    Cristina Has
    Department of Dermatology, University Medical Center Freiburg, Freiburg 79104, Germany
    Am J Pathol 175:1442-52. 2009
    ..with small-interfering RNA, protein, and imaging studies, to uncover new functions for kindlin-1 in keratinocytes and to discern the molecular pathology of KS...
  84. pmc TRPV3 in keratinocytes transmits temperature information to sensory neurons via ATP
    Sravan Mandadi
    Division of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institute for Physiological Sciences, Okazaki, Japan
    Pflugers Arch 458:1093-102. 2009
    Transient receptor potential V3 (TRPV3) and TRPV4 are heat-activated cation channels expressed in keratinocytes. It has been proposed that heat-activation of TRPV3 and/or TRPV4 in the skin may release diffusible molecules which would ..
  85. pmc Establishment of human papillomavirus infection requires cell cycle progression
    Dohun Pyeon
    McArdle Laboratory for Cancer Research, University of Wisconsin Madison, Madison, WI, USA
    PLoS Pathog 5:e1000318. 2009
    ..Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must ..
  86. pmc E6 proteins from multiple human betapapillomavirus types degrade Bak and protect keratinocytes from apoptosis after UVB irradiation
    Michael P Underbrink
    Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 1024, USA
    J Virol 82:10408-17. 2008 is unknown if the ability to degrade Bak is limited to certain beta-HPV types or whether E6 expression in keratinocytes affects other proteins important for apoptosis signaling...
  87. pmc Activation of TLR2 by a small molecule produced by Staphylococcus epidermidis increases antimicrobial defense against bacterial skin infections
    Yuping Lai
    Division of Dermatology, Department of Medicine, University of California, San Diego and VA San Diego Healthcare System, San Diego, California 92161, USA
    J Invest Dermatol 130:2211-21. 2010
    ..the commensal microorganism Staphylococcus epidermidis may enhance production of antimicrobial peptides by keratinocytes and thus augment skin defense against infection...
  88. ncbi Cellular mechanisms regulating human melanogenesis
    H Y Park
    Department of Dermatology, Boston University School of Medicine, 609 Albany Street, Boston, MA 02118, USA
    Cell Mol Life Sci 66:1493-506. 2009
    ..Mature melanosomes are transferred to neighboring keratinocytes and are arranged in a supranuclear cap, protecting the DNA against incident ultraviolet light (UV) irradiation...
  89. pmc Physiological factors that regulate skin pigmentation
    Yuji Yamaguchi
    Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
    Biofactors 35:193-9. 2009
    ..melanosome biogenesis, transport and transfer, melanogenic regulators in melanocytes, and factors derived from keratinocytes, fibroblasts, endothelial cells, hormones, inflammatory cells, and nerves...
  90. ncbi The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders
    M Frohm
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S 171 77 Stockholm, Sweden
    J Biol Chem 272:15258-63. 1997
    ..By in situ hybridization and immunohistochemistry the transcript and the peptide were located in keratinocytes throughout the epidermis of the inflammatory regions...
  91. ncbi Mechanical stress induces profound remodelling of keratin filaments and cell junctions in epidermolysis bullosa simplex keratinocytes
    David Russell
    Cancer Research UK Cell Structure Research Group, School of Life Sciences, MSI WTB complex, University of Dundee, Dundee, DD1 5EH, UK
    J Cell Sci 117:5233-43. 2004
    ..The results suggest that maintenance of desmosomes and hemidesmosomes may require some tension, normally mediated by keratin attachments...
  92. ncbi 1,25-Dihydroxyvitamin D3 inhibits ultraviolet B-induced apoptosis, Jun kinase activation, and interleukin-6 production in primary human keratinocytes
    Petra De Haes
    Laboratory for Experimental Medicine and Endocrinology LEGENDO, Gasthuisberg, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
    J Cell Biochem 89:663-73. 2003
    We investigated the capacity of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] to protect human keratinocytes against the hazardous effects of ultraviolet B (UVB)-irradiation, recognized as the most important etiological factor in the ..
  93. ncbi ERK1/2 regulates epidermal chemokine expression and skin inflammation
    Saveria Pastore
    Laboratory of Immunology, Istituto Dermopatico dell Immacolata, Instituto di Ricovero e Cura a Carattere Scientifico, Roma, Italy
    J Immunol 174:5047-56. 2005
    ..TNF-alpha is a major inducer of proinflammatory mediators in keratinocytes. We have recently observed that epidermal growth factor receptor (EGFR) signaling affects TNF-alpha-driven ..
  94. ncbi Areca (betel) nut extract activates mitogen-activated protein kinases and NF-kappaB in oral keratinocytes
    Shu Chun Lin
    Institute of Oral Biology, School of Dentistry, National Yang Ming University, Peitou, Taipei, Taiwan
    Int J Cancer 116:526-35. 2005
    ..We examined the activation of these signaling pathways in OECM-1 and SAS oral keratinocytes, treated with ripe areca nut extract (ANE). In both cells, a rapid increase in JNK1 activity at 0...
  95. ncbi Knockdown of filaggrin impairs diffusion barrier function and increases UV sensitivity in a human skin model
    Michael Mildner
    Department of Dermatology, Medical University of Vienna, Vienna, Austria
    J Invest Dermatol 130:2286-94. 2010
    ..In addition, our results challenge the role of filaggrin in intermediate filament aggregation and establish a link between filaggrin and endogenous UVB protection...
  96. ncbi Impaired PI3K/Akt activation-mediated NF-kappaB inactivation under elevated TNF-alpha is more vulnerable to apoptosis in vitiliginous keratinocytes
    Nan Hyung Kim
    Department of Dermatology, Dongguk University School of Medicine, Gyenggi do, South Korea
    J Invest Dermatol 127:2612-7. 2007
    ..B (PI3K/Akt) signaling pathway, was significantly higher in depigmented epidermis, implying that vitiliginous keratinocytes may be more susceptible to TNF-alpha-mediated apoptosis through impaired Akt and NF-kappaB activation...
  97. pmc Linking the p53 tumour suppressor pathway to somatic cell reprogramming
    Teruhisa Kawamura
    Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 460:1140-4. 2009
    ..These results provide insights into reprogramming mechanisms and suggest new routes to more efficient reprogramming while minimizing the use of oncogenes...
  98. ncbi The epidermal growth factor receptor system in skin repair and inflammation
    Saveria Pastore
    Laboratory of Tissue Engineering and Cutaneous Physiopathology, Istituto Dermopatico dell Immacolata, IRCCS, Via Monti di Creta 104, Rome, Italy
    J Invest Dermatol 128:1365-74. 2008
  99. pmc Epidermal stem cells are defined by global histone modifications that are altered by Myc-induced differentiation
    Michaela Frye
    Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge, United Kingdom
    PLoS ONE 2:e763. 2007
    ..We conclude that Myc-induced chromatin modifications play a major role in Myc-induced exit from the stem cell compartment...
  100. pmc Selective antimicrobial action is provided by phenol-soluble modulins derived from Staphylococcus epidermidis, a normal resident of the skin
    Anna L Cogen
    Division of Dermatology, Department of Medicine, University of California San Diego, VA San Diego Health Care System, San Diego, California, USA
    J Invest Dermatol 130:192-200. 2010
    ..Thus, these data suggest that the production of PSMgamma and PSMdelta by S. epidermidis can benefit cutaneous immune defense by selectively inhibiting the survival of skin pathogens while maintaining the normal skin microbiome...
  101. ncbi IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not
    Kerstin Wolk
    Interdisciplinary Group of Molecular Immunopathology, Dermatology Medical Immunology, University Hospital Charite, Chariteplatz 1, 10117, Berlin, Germany
    J Mol Med (Berl) 87:523-36. 2009
    ..This cutaneous phenotype may be caused by the direct influence of IL-22 on keratinocytes, since this cytokine did not affect skin fibroblasts, endothelial cells, melanocytes, or adipocytes...

Research Grants79

  1. Role of CRH in skin physiology and pathology
    Andrzej Slominski; Fiscal Year: 2004
    ..To define local mechanisms regulating the expression of CRH in normal melanocytes and keratinocytes; 2...
  2. Anti-tumor properties of curcumin in oral cancers: role of thioredoxin reductase
    STEPHEN WILLIAM TUTTLE; Fiscal Year: 2010
    ..squamous carcinoma cell line FaDu compared to either an oral leukoplakia cell line MSK-Leuk1 or nontransformed keratinocytes. In specific aim 1, we plan to knockdown TxRd1 levels in FaDu cells using shRNA to the 3'UTR of the human ..
  3. Role of NGF in inflammatory and proliferative cascades of psoriatic disease
    Siba P Raychaudhuri; Fiscal Year: 2012
    ..Psoriatic keratinocytes (KC) express high level of NGF/NGF-R and NGF is mitogeic to KC...
  4. Targeting Galectin-3 with novel drugs for treatment of eczema
    Fu Tong Liu; Fiscal Year: 2010
    ..and inflammatory pathways that include T cells, dendritic cells, mast cells and eosinophils, as well as keratinocytes. Treatment of eczema continues to be a challenge, especially in patients with severe disease...
  5. Targeting p53-Dependent Repigmentation in Vitiligo
    TAMARA G TERZIAN; Fiscal Year: 2013
    ..She plans to investigate the role of the p53 pathway in regulating the secretion of factors from keratinocytes and how these factors affect melanocyte behavior (proliferation, migration and differentiation)...
    Tatiana Efimova; Fiscal Year: 2013, obtained since the previous review of this application, show that oncogenic ras-transformed p384-null keratinocytes formed smaller skin tumors in orthotopic skin grafts to p384 intact hosts, compared with transformed wild-type ..
  7. Role of beta-endorphin in cancer therapy induced fatigue
    David E Fisher; Fiscal Year: 2013
    ..Our lab studies skin signaling which mediates UV induced pigmentation. UV damages DNA in keratinocytes, thereby stabilizing p53 which stimulates expression of pro-opiomelanocortin (POMC)...
  8. Somatic Stem Cells in Engineered Human Skin
    Steven Boyce; Fiscal Year: 2009 substitutes (CSS) consisting of a collagen-based sponge populated with cultured human fibroblasts and keratinocytes. This model of engineered human skin develops a keratinized epithelium, basement membrane, and has a dermal ..
  9. Testing the Therapeutic Potential of iPS Cells for Inherited Skin Diseases
    Jakub Tolar; Fiscal Year: 2013
    ..of an inherited skin disease where there would be a "natural selection" for genetically corrected iPSC-derived keratinocytes if they were seeded into areas prone to blistering...
  10. PKC delta and cell renewal in irradiated taste epithelium
    MARY ELAINE REYLAND; Fiscal Year: 2012
    ..PKC4 has also been implicated in maintenance of cell cycle arrest required for DNA repair in UV damaged human keratinocytes. Thus, we will test the hypothesis that loss of PKC4 protects taste progenitor cells from death, and/or ..
  11. Regulation of Human Papillomavirus Replication via Cell Signaling Pathways
    ANASTACIA GRIEGO; Fiscal Year: 2013
    ..approaches and will evaluate the ability of EGFR-pathway inhibitors to decrease viral activities in human keratinocytes containing episomal or integrated high-risk HPVs...
  12. Arsenic co-carcinogenesis with UVR: nitrosation and oxidation of target proteins
    Ke Jian Liu; Fiscal Year: 2013
    ..generation on the activity of two DNA repair proteins (XPA and PARP-1), DNA repair and genotoxicity in keratinocytes. Genetic and pharmacologic disruption of iNOS and NOX will define which pathway(s) are involved in arsenic-..
  13. A reconstructed skin model for development of treatments for albinism
    Seth J Orlow; Fiscal Year: 2010
    ..mouse and human melanocytes, these experiments do not address the issue of skin penetration and metabolism by keratinocytes, which may render the compound inert or worse, produce a toxic by-product...
  14. Biologic Activities of IL-36 Cytokines in Psoriasis
    Andrew Johnston; Fiscal Year: 2013
    ..and hyperproliferative skin disease driven by interactions of T cell, antigen-presenting cells (APC), keratinocytes and cytokines...
  15. 3D Skin Model to Test Toxic and Sensitizing Potentials of Environmental Chemicals
    Akira Takashima; Fiscal Year: 2010
    ..We have identified ATP release from keratinocytes (KCs) as an initial and causative event in the pathogenesis of irritant contact dermatitis...
  16. Mouse models for esophageal Cox-2 oxidative stress and DNA damage
    John P Lynch; Fiscal Year: 2013
    ..When we express Cox-2 in normal human esophageal keratinocytes we observe the development of intestinal mucin-filled cysts...
  17. Mechanisms of cancer initiation by TRIM32
    Molly F Kulesz-Martin; Fiscal Year: 2012
    ..Piasy is a pro- apoptotic factor, inducing apoptosis in CML cells, human fibroblasts and mouse keratinocytes. We show that Trim32 protects keratinocytes from apoptosis induced by UVB and synergized by TNFa...
  18. Targeting Tight Junctions To Treat Mucositis
    FREDERICK GARY TOBACK; Fiscal Year: 2010
    ..The synthetic 21-mer peptide stimulates growth of human keratinocytes (HaCaT line) used to model the oral mucosa, and also has protective, and motogenic properties in cell culture...
  19. Tpl2 in Carcinogenesis-Related Inflammation
    KATHLEEN LEIGH DECICCO-SKINNER; Fiscal Year: 2011 determine which members of the COX-2 pathway alter proliferation, migration and invasiveness of Tpl2-/- keratinocytes. Specifically, in this aim we will (a) determine the potential of the wildtype and Tpl2-/- keratinocytes to ..
  20. Circadian Clock Regulation in Skin
    Bogi Andersen; Fiscal Year: 2013
    PROJECT SUMMARY/ABSTRACT Using genetic mouse models, we found that the circadian clock within keratinocytes is required for the time-of- day dependent variation in interfollicular epidermal cell proliferation, which seems to be ..
  21. Cytokine Signaling in Neurons: Inflammation, Pain and Pruritis
    Martin Steinhoff; Fiscal Year: 2013
    ..In addition, keratinocytes, which express classical "neuronal" receptors and release factors that subsequently modulate the function of ..
    LARRY FEIG; Fiscal Year: 2009
    ..In keratinocytes of the epithelium, RalA inhibits tumorigenesis, since suppression of RalA expression enhances tumor ..
  23. Discovery of Novel Anti-Inflammatory Phytochemicals on Human Cell Platforms
    ERIK MILLS SCHWIEBERT; Fiscal Year: 2010
    ..DBM will utilize a deep panel of immortalized human cells derived from skin (keratinocytes), respiratory system (nasal, airway and lung epithelial cells) and renal system (proximal tubule, cortical, ..
  24. Role of dyskerin in oral epithelial homeostasis
    Faizan Alawi; Fiscal Year: 2013
    ..expression peaks during mitosis, the protein localizes to distinct sub-cellular structures in mitotic oral keratinocytes, and acute loss of dyskerin function triggers G2/M arrest and leads to the accumulation of atypical mitoses ..
  25. Modeling oxidative stress and DNA damage using GI organotypic culture systems
    John P Lynch; Fiscal Year: 2013
    ..When we ectopically express Cox-2 in normal human esophageal keratinocytes, we observe the development of intestinal mucin-filled cysts...
  26. Plexin signalling in melanocyte biology and melanoma progression
    Glynis A Scott; Fiscal Year: 2013
    ..photoprotection of the skin from ultraviolet radiation (UVR) through the production and transfer of melanin to keratinocytes [1]...
    David J Feith; Fiscal Year: 2013
    ..Next, primary keratinocytes from our transgenic models will be utilized to measure proliferation, migration, and markers of ..
  28. Role of exogenous melatonin in skin biology
    Andrzej T Slominski; Fiscal Year: 2013
    ..Therefore, we are proposing: 1. To define the protective role of melatonin in human epidermis using epidermal keratinocytes and melanocytes cultured in vitro and human skin explants histocultured ex-vivo;2...
  29. 3D human skin models
    Meenhard Herlyn; Fiscal Year: 2010
    ..and immune cells that are all embedded in collagen type I;2) 'epidermis'consisting of multilayered keratinocytes at distinct differentiation stages and melanocytes, which reside in the basal layer and attach to the ..
  30. Targeting Injury Pathways to Counteract Pulmonary Agent and Vesicant Toxicity
    Sven Eric Jordt; Fiscal Year: 2013
    ..TRPV3, a TRP ion channel in keratinocytes, is a candidate mediator of cutaneous injury by vesicants and corrosive electrophiles...
  31. Fanconi Anemia as a Model for Susceptibility to Human Papillomavirus Infection
    ..Further, the observed increased oral HPV prevalence in individuals with FA compared to controls indicates that keratinocytes deficient in FA-related genes uniquely support HPV infection and/or replication...
  32. Function of the Ras Related Ral Protein
    LARRY FEIG; Fiscal Year: 2013
    ..We found that RalA plays a cell-type dependent role in Ras-mediated squamous cell carcinoma. In keratinocytes of the epithelium, RalA inhibits, rather than supports tumorigenesis, since suppression of RalA expression ..
  33. Biomarkers of Aggressive Oral Cancer
    ..Furthermore, compared to normal oral keratinocytes, HNSCC cells also show elevated levels of glutamic acid...
  34. Autophagy in epidermal melanocyte: a protective or a destructive role?
    Vijayasaradhi Setaluri; Fiscal Year: 2013
    ..Is autophagic cell death a normal homeostatic mechanism that maintains epidermal melanin unit? What role do keratinocytes play in sensitivity of melanocytes to autophagy? What is the role of Atg5 and Atg7 in sensitivity of ..
  35. Development of Adult Pluripotent Very Small Embryonic Like (VSEL) Stem Cells to T
    DENIS OVEREND RODGERSON; Fiscal Year: 2013
    ..showed the BMSCs could effectively heal wounded skin and facilitate production of new blood vessels, and keratinocytes. Autologous BMSCs were also found effective in treating non-healing human chronic wounds in clinical studies...
  36. Role of Protein Kinase D in Skin Epithelia
    Soosan Ghazizadeh; Fiscal Year: 2012
    ..However, our recent studies showing that differentiated keratinocytes can and do revert to self renewing stem cells challenges this long held view...
  37. Calcium-sensing Receptor and Keratinocyte Differentiation
    Chia Ling Tu; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Epidermis consists of multiple layers of keratinocytes, which differentiate and produce a permeability barrier that provides protection against environmental insults...
  38. Defensin-induced adaptive immunity to HagB
    Kim A Brogden; Fiscal Year: 2013
    ..determine the ability of HBD3 to attenuate the pro- inflammatory cytokine response and MAPK response of human keratinocytes, monocytes, and myeloid dendritic cells to rHagB and rFimA...
  39. Stat3 in Epitherlial Carcinogenesis
    John DiGiovanni; Fiscal Year: 2012
    ..During tumor initiation, further studies revealed that Stat3 is required for survival of DNA damaged keratinocytes, including those located in the hair follicle bulge region (i.e., stem cell compartment)...
  40. HPV, Tumor Metabolism and Radiosensitivity in Head and Neck Cancer
    Hyeong Reh Choi Kim; Fiscal Year: 2013
    ..A previous study showed that transfection of the dominant-negative p53 mutant into oral keratinocytes, mimicking smoking-associated cancer, results in upregulation of hypoxia signaling (HIF1) pathway, which in ..
  41. Keratinocyte regulation of skin immunity
    Anthony A Gaspari; Fiscal Year: 2013
    ..We selected this skin condition because it is a common skin disease in Veterans. We hypothesize that Keratinocytes (KC) are tolerigenic Antigen presenting cells for Natural killer (NK)T-cells...
  42. Cellular Determinants of Ah Receptor Signaling
    Thomas R Sutter; Fiscal Year: 2013
    ..homeostasis and identify one mechanism by which EGFR signaling can repress AHR-mediated transcription in keratinocytes. We propose to test the hypothesis that in the epidermis, TCDD-activated AHR disrupts the epidermal barrier by ..
  43. Role of vitamin D receptor in DNA repair
    Dennis H Oh; Fiscal Year: 2013
    ..Using mouse epidermal sheets as well as cultured human and mouse keratinocytes in which VDR is deficient, we will determine if VDR induction is a general response to multiple forms of DNA ..
  44. Apigenin restores TSP-1 expression in UVB-irradiated keratinocytes
    Jill C Pelling; Fiscal Year: 2013
    ..Our preliminary results show that Api blocks downregulation of TSP-1 by UVB in cultured keratinocytes and skin in vivo...
  45. Characterization of Enhancers in the Epidermal Differentiation Complex
    CRISTINA DE GUZMAN STRONG; Fiscal Year: 2012
    ..will determine colocalization of the CNS EDC to open chromatin using DNasel hypersensitivity assays in mouse keratinocytes and barrier deficient mouse models. These aims will be completed during the mentored phase under Dr...
  46. Cpdm: Cloning a Gene That Regulates Eosinophil Function
    JOHN PAUL SUNDBERG; Fiscal Year: 2013
    ..To define how each cell type responds, we will selectively inactivate Sharpin in keratinocytes, fibroblasts, endothelial cells, adipose tissue, various subsets of lymphocytes, etc...
  47. Development of Extracellular Heat Shock Protein-90 as a Novel Topical Wound Heali
    Wei Li; Fiscal Year: 2013
    ..We found that both human keratinocytes and dermal fibroblasts rapidly secrete Hsp90a...
  48. Regulation of orofacial ectodermal polarity by the CLP protein, IRF6
    EMILY YIN CHU; Fiscal Year: 2013
    ..homology with other IRFs, IRF6 has been predicted to act as a transcription factor, although studies in keratinocytes have found IRF6 primarily in the cytoplasm...
  49. Genome-wide SNP association in psoriasis
    ANNE MARY BOWCOCK; Fiscal Year: 2012
    ..Ps/PsA associated mutations enhanced NF- kB activation and altered the transcriptome of keratinocytes, leading to the production of chemokines and other psoriasis-associated inflammatory markers...
    RICHARD ARTHUR CHOLE; Fiscal Year: 2013
    ..We will examine the effect of lipopolysaccharide in the proliferation and differentiation of keratinocytes in vitro using an immortalized cell line, primary human and primary mouse keratinocytes...
  51. Role of MicroRNA 363 in HPV-positive oral cancer
    Saleem A Khan; Fiscal Year: 2013
    ..HPV-16 positive OP cancer tissues compared to HPV-negative OPSCC tissues, normal oral mucosa and normal oral keratinocytes (NOKs)...
    Louise T Chow; Fiscal Year: 2013
    ..HPVs infect basal keratinocytes, while the productive phase occurs only in the differentiated strata of squamous epithelia...
  53. The Role of Protein Kinase D in Epidermal Tumorigenesis
    Wendy B Bollag; Fiscal Year: 2013
    ..BCCs, which make up approximately 80% of the NMSCs, arise from basal keratinocytes in the epidermis of the skin...
  54. Small Interfering RNAs: Inhibition of Oral Carcinogenesis in a Mouse Model
    Lorraine J Gudas; Fiscal Year: 2010
    ..and cyclin D1 and to test their specificity and potential off-target effects by using cultured primary mouse keratinocytes. The results from these experiments will allow us to determine the most appropriate siRNAs to be used in ..
  55. The Role of IgE in Autoimmune Skin Diseases
    Janet A Fairley; Fiscal Year: 2013
    ..effects via multiple mechanisms that involve binding of the IgE either to BP180 on the surface of epidermal keratinocytes or to its high affinity receptor, Fc5RI, on mast cells and potentially eosinophils...
  56. Regulation of Nucleotide Excision Repair by Proteolysis
    Pengbo Zhou; Fiscal Year: 2013
    ..the cyclin-dependent kinase inhibitor p21/CIP1/WAF1 in CUL-4A-/- and DDB1-/- mice, as well as in MEF cells and keratinocytes derived from these mice...
  57. Epidermal stem cell properties in mice with altered polyamines
    Lisa M Shantz; Fiscal Year: 2010
    ..Aim 2 will use organotypic raft cultures of human keratinocytes expressing MEK, CD1 and/or AZ...
  58. microRNA Control of Wound Healing
    Chandan K Sen; Fiscal Year: 2013
    ..Hypothesis 1.3: Dicer knockdown compromises proliferation and migration of keratinocytes. AIM2: Determine the significance of miR-1 dependent molecular mechanisms regulating wound re-..
  59. Microtubule dynamics during cell polarity and migration
    Torsten Wittmann; Fiscal Year: 2012
    ..RELEVANCE: Collective cell migration is essential for many morphogenetic movements and the sheet migration of keratinocytes across the basement membrane after injury...
  60. Skin Defense by Antimicrobial Peptides
    Richard L Gallo; Fiscal Year: 2012
    ..Specifically, our aims are to: 1. Determine how glucocorticods alter antimicrobial peptide production in keratinocytes. Thus addressing the question: What AMPs are altered in keratinocytes exposed to glucocorticoids? 2...
  61. Mechanisms of Human Dermal Fibroblast Migration
    Wei Li; Fiscal Year: 2013
    ..bed during wound healing? Specifically, what factor(s) is responsible for the lateral migration of epidermal keratinocytes over the wound bed to close the wound and inward migration of dermal fibroblasts and microvascular endothelial ..
  62. Role of poly (ADP-ribose)in the Repair of Ultraviolet Induced DNA Damage
    BRENEE SHEMEIR KING; Fiscal Year: 2012
    ..PARP leads to the retention of pyrimidine dimers and other photolesions and we find similar results in human keratinocytes. While the data supporting PARP-1's involvement in NER is increasing, the mechanism of action has yet to ..
  63. Mechanisms of Genetic Reversion in Ichthyosis With Confetti
    Keith A Choate; Fiscal Year: 2013
    ..competition assays in a human skin equivalent graft model in which varying proportions of revertant or normal keratinocytes are mixed with mutant IWC or EI cells and resulting epidermis is assayed for composition by each cell type ..
  64. Role of vitamin D and calcium signaling in wound healing
    DANIEL DAVID BIKLE; Fiscal Year: 2013
    ..Stem cells in the bulge of the hair follicle provide keratinocytes not only for hair follicle formation but also for the reepithelialization of the epidermis following wounding...
  65. Protein Kinase D and Epidermal Structure and Function
    Wendy B Bollag; Fiscal Year: 2010
    ..BCCs, which make up approximately 80% of the NMSCs, arise from basal keratinocytes in the epidermis of the skin...
  66. Ligand independent signaling by VDR in Keratinocytes
    Paul N MacDonald; Fiscal Year: 2010
    ..The focus of this research proposal is on the vitamin D endocrine system in epidermal keratinocytes and, specifically, on the use of murine models of the vitamin D endocrine system as tools to explore the in ..
    RICHARD ECKERT; Fiscal Year: 2004
    ..The target proteins include regulators of cell proliferation and differentiation. Although keratinocytes express eight S100 proteins, little information is available regarding S100 protein function in keratinocytes...
  68. Laminin-based protein therapeutics for junctional epidermolysis bullosa
    Vitali Alexeev; Fiscal Year: 2009
    ..the lamina lucida of the cutaneous basement membrane zone (BMZ) and is associated with weak adhesion of basal keratinocytes to dermal anchoring fibrils...
  69. Role of senescent fibroblasts in UVB-induced carcinogenesis
    Dan F Spandau; Fiscal Year: 2010
    ..Using normal human keratinocytes grown in vitro, activated IGF-1Rs protect keratinocytes from UVB-induced apoptosis;however, while UVB-..
  70. Role of Wnt signaling in Cervical Cancer Pathogenesis
    Aykut Uren; Fiscal Year: 2010
    ..Our experimental model of cervical carcinoma uses HPV-immortalized primary human keratinocytes. In an in vitro experimental model, malignant transformation of HPV-immortalized keratinocytes can be achieved ..
    ROBERT LAVKER; Fiscal Year: 2001
    The protective function of the epidermis depends critically on the normal differentiation of the keratinocytes. Cell to cell adhesion is essential in this process...
    SERGEI GRANDO; Fiscal Year: 2001
    ..BACKGROUND: Closure of skin wounds involves the migration of keratinocytes into the wound bed...
    ANTHONY CAMPAGNARI; Fiscal Year: 2000
    ..Dr. Campagnari's hypothesis is that the oligosaccharide of H. ducrei LOS binds to a surface structure on keratinocytes. He also hypothesizes that the eukaryotic structure mediating such binding is in the family of the Galactose ..
  74. Evaluation of siRNA uptake and functional activity in a human organotypic skin mo
    Roger L Kaspar; Fiscal Year: 2010
    ..stratum corneum barrier and also provides a hydrodynamic pressure that appears to facilitate siRNA uptake by keratinocytes. We, and others, have developed patient-friendly technologies that allow siRNA to be delivered across the ..
  75. Role for DKC1 in cell proliferation and transformation
    Faizan Alawi; Fiscal Year: 2009
    ..of c-MYC is one of only five distinct molecular alterations needed for transformation of primary oral keratinocytes.Yet, the molecular mechanisms by which c-MYC induces cellular transformation remain poorly understood...
    ..extremely resistant to UV carcinogenesis and phototoxicity, and their skin contains a high number of apoptotic keratinocytes compared to CD1+/+ mice...
  77. Amphiregulin in Psoriatic Epidermal Hyperplasia
    JAMES TILFORD ELDER; Fiscal Year: 2010
    ..However, the mechanism by which immunologic activation triggers epidermal hyperplasia remains unknown. Keratinocytes overexpress multiple ErbB1 ligands in psoriasis, including amphiregulin (AR), TGF-a, and HB- EGF...
  78. IkB Kinase alpha (IKKalpha): Role in Skin Carcinogenesis
    Yinling Hu; Fiscal Year: 2007
    ..Our preliminary results show that the immortalized IKKalpha-/- keratinocytes are able to form cell colonies in soft agar and grow into poorly differentiated spindle cell carcinomas in ..
  79. The role of E-cadherin in photocarcinogenesis
    Sabine M Brouxhon; Fiscal Year: 2010
    ..exploratory-developmental (R21) research grant proposal is to investigate whether loss of E-cadherin in basal keratinocytes and their progeny is facilitative in the development of ultraviolet (UV) lightinduced skin squamous cell ..