transforming growth factor beta

Summary

Summary: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.

Top Publications

  1. ncbi SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7
    Gareth J Inman
    Laboratory of Developmental Signalling, Cancer Research UK London Research Institute, Lincoln s Inn Fields Laboratories, London, UK
    Mol Pharmacol 62:65-74. 2002
  2. pmc TGFbeta in Cancer
    Joan Massague
    Cancer Biology and Genetics Program, and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell 134:215-30. 2008
  3. ncbi Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells
    Estelle Bettelli
    Center for Neurologic Diseases, Beth Israel Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nature 441:235-8. 2006
  4. ncbi Smad-dependent and Smad-independent pathways in TGF-beta family signalling
    Rik Derynck
    Department of Growth and Development, University of California at San Francisco, San Francisco, California 94143 0640, USA
    Nature 425:577-84. 2003
  5. ncbi Mechanisms of TGF-beta signaling from cell membrane to the nucleus
    Yigong Shi
    Department of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA
    Cell 113:685-700. 2003
  6. ncbi Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member
    A C McPherron
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nature 387:83-90. 1997
  7. ncbi Smad transcription factors
    Joan Massague
    Cancer Biology and Genetics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Genes Dev 19:2783-810. 2005
  8. ncbi Bone morphogenetic proteins
    Di Chen
    School of Medicine and Dentistry, Department of Orthopaedics, University of Rochester, Rochester, NY 14642, USA
    Growth Factors 22:233-41. 2004
  9. pmc Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3
    Wanjun Chen
    Cellular Immunology Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 198:1875-86. 2003
  10. ncbi TGF-beta and epithelial-to-mesenchymal transitions
    Jiri Zavadil
    Department of Pathology, NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, USA
    Oncogene 24:5764-74. 2005

Detail Information

Publications321 found, 100 shown here

  1. ncbi SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7
    Gareth J Inman
    Laboratory of Developmental Signalling, Cancer Research UK London Research Institute, Lincoln s Inn Fields Laboratories, London, UK
    Mol Pharmacol 62:65-74. 2002
    ..b>Transforming growth factor beta (TGF-beta) is a member of a large family of pleiotropic cytokines that are involved in many ..
  2. pmc TGFbeta in Cancer
    Joan Massague
    Cancer Biology and Genetics Program, and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell 134:215-30. 2008
    The transforming growth factor beta (TGFbeta) signaling pathway is a key player in metazoan biology, and its misregulation can result in tumor development...
  3. ncbi Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells
    Estelle Bettelli
    Center for Neurologic Diseases, Beth Israel Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nature 441:235-8. 2006
    ..Our data demonstrate a dichotomy in the generation of pathogenic (T(H)17) T cells that induce autoimmunity and regulatory (Foxp3+) T cells that inhibit autoimmune tissue injury...
  4. ncbi Smad-dependent and Smad-independent pathways in TGF-beta family signalling
    Rik Derynck
    Department of Growth and Development, University of California at San Francisco, San Francisco, California 94143 0640, USA
    Nature 425:577-84. 2003
    ..Other signalling pathways further regulate Smad activation and function. In addition, TGF-beta receptors activate Smad-independent pathways that not only regulate Smad signalling, but also allow Smad-independent TGF-beta responses...
  5. ncbi Mechanisms of TGF-beta signaling from cell membrane to the nucleus
    Yigong Shi
    Department of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA
    Cell 113:685-700. 2003
    ..This article reviews these latest advances and presents our current understanding on the mechanisms of TGF-beta signaling from cell membrane to the nucleus...
  6. ncbi Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member
    A C McPherron
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nature 387:83-90. 1997
    ..These results suggest that GDF-8 functions specifically as a negative regulator of skeletal muscle growth...
  7. ncbi Smad transcription factors
    Joan Massague
    Cancer Biology and Genetics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Genes Dev 19:2783-810. 2005
    ..Our growing understanding of TGFbeta signaling through the Smad pathway provides general principles for how animal cells translate complex inputs into concrete behavior...
  8. ncbi Bone morphogenetic proteins
    Di Chen
    School of Medicine and Dentistry, Department of Orthopaedics, University of Rochester, Rochester, NY 14642, USA
    Growth Factors 22:233-41. 2004
    Bone morphogenetic proteins (BMPs) are multi-functional growth factors that belong to the transforming growth factor beta (TGFbeta) superfamily...
  9. pmc Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3
    Wanjun Chen
    Cellular Immunology Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 198:1875-86. 2003
    ..and intracellular CTLA-4+ can be achieved through costimulation with T cell receptors (TCRs) and transforming growth factor beta (TGF-beta)...
  10. ncbi TGF-beta and epithelial-to-mesenchymal transitions
    Jiri Zavadil
    Department of Pathology, NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, USA
    Oncogene 24:5764-74. 2005
    ..Here we will review the distinct physiological contexts of EMT and the underlying molecular signaling networks controlled by TGF-beta...
  11. pmc Liver fibrosis
    Ramon Bataller
    Liver Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clinic, Institut d Investigació Biomèdiques August Pi i Sunyer IDIBAPS, Barcelona, Catalonia, Spain
    J Clin Invest 115:209-18. 2005
    ..This review summarizes recent progress in the study of the pathogenesis and diagnosis of liver fibrosis and discusses current antifibrotic strategies...
  12. ncbi TGF-beta signaling in tumor suppression and cancer progression
    R Derynck
    Department of Growth and Development, University of California at San Francisco, San Francisco, California, USA
    Nat Genet 29:117-29. 2001
    ..Among these, transforming growth factor beta (TGF-beta) and its signaling effectors act as key determinants of carcinoma cell behavior...
  13. ncbi TGF-beta signal transduction
    J Massague
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Annu Rev Biochem 67:753-91. 1998
    The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms...
  14. ncbi TGF-beta-induced epithelial to mesenchymal transition
    Jian Xu
    Department of Cell and Tissue Biology, Programs in Cell Biology and Developmental Biology, University of California San Francisco, San Francisco, CA, USA
    Cell Res 19:156-72. 2009
    ..In this review, we will discuss the induction of EMT in response to TGF-beta, and focus on the underlying signaling and transcription mechanisms...
  15. pmc IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells
    Thomas Korn
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 448:484-7. 2007
    ..We show that an IL-2 cytokine family member, IL-21, cooperates with TGF-beta to induce T(H)17 cells in naive Il6-/- T cells and that IL-21-receptor-deficient T cells are defective in generating a T(H)17 response...
  16. ncbi Molecular definition of breast tumor heterogeneity
    Michail Shipitsin
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Cell 11:259-73. 2007
    ..Our data suggest prognostic relevance of CD44+ cells and therapeutic targeting of distinct tumor cell populations...
  17. pmc Non-Smad pathways in TGF-beta signaling
    Ying E Zhang
    Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell Res 19:128-39. 2009
    ..This review focuses on recent advances in the understanding of the molecular and biochemical mechanisms of non-Smad pathways. In addition, functions of these non-Smad pathways are also discussed...
  18. ncbi The regulation of TGFbeta signal transduction
    Aristidis Moustakas
    Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
    Development 136:3699-714. 2009
    b>Transforming growth factor beta (TGFbeta) pathways are implicated in metazoan development, adult homeostasis and disease...
  19. ncbi Mechanisms of foxp3+ T regulatory cell-mediated suppression
    Ethan M Shevach
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 30:636-45. 2009
    ..An increase in our understanding of Treg cell suppressor mechanisms will offer an insight into how Treg cell function can be manipulated either positively or negatively in vivo...
  20. ncbi TGF-beta signalling from cell membrane to nucleus through SMAD proteins
    C H Heldin
    Ludwig Institute for Cancer Research, Biomedical Centre, Uppsala, Sweden
    Nature 390:465-71. 1997
    ..Inhibitory SMADs have been identified that block the activation of these pathway-restricted SMADs...
  21. ncbi Endothelial-to-mesenchymal transition contributes to cardiac fibrosis
    Elisabeth M Zeisberg
    Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Nat Med 13:952-61. 2007
    ..Our findings show that EndMT contributes to the progression of cardiac fibrosis and that rhBMP-7 can be used to inhibit EndMT and to intervene in the progression of chronic heart disease associated with fibrosis...
  22. pmc SMAD proteins control DROSHA-mediated microRNA maturation
    Brandi N Davis
    Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    Nature 454:56-61. 2008
    ..The transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) family of growth factors orchestrates fundamental ..
  23. ncbi TGF-beta signaling and the fibrotic response
    Andrew Leask
    Centre for Rheumatology, Department of Medicine, Royal Free and University College Medical School, Rowland Hill St, London, UK NW3 2PF
    FASEB J 18:816-27. 2004
    ....
  24. ncbi Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer
    Brian Bierie
    Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Nat Rev Cancer 6:506-20. 2006
    ..The complex nature of TGFbeta signalling and crosstalk in the tumour microenvironment presents a unique challenge, and an opportunity to develop therapeutic intervention strategies for targeting cancer...
  25. ncbi Epithelial-mesenchymal transitions in development and pathologies
    Jean Paul Thiery
    Unite Mixte de Recherche 144, Centre National Recherche Scientifique, Institut Curie, 26 Rue d Ulm, 75248 Paris Cedex 05, France
    Curr Opin Cell Biol 15:740-6. 2003
    ..Current studies further emphasise the critical importance of EMT and provide a better molecular and functional definition of mesenchymal cells and how they emerged >500 million years ago as a key event in evolution...
  26. ncbi Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor?
    Maria A Curotto de Lafaille
    Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine of the Skirball Institute, and Department of Pathology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    Immunity 30:626-35. 2009
    ....
  27. ncbi TLR4 enhances TGF-beta signaling and hepatic fibrosis
    Ekihiro Seki
    Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA
    Nat Med 13:1324-32. 2007
    ..Accordingly, Myd88-deficient mice have decreased hepatic fibrosis. Thus, modulation of TGF-beta signaling by a TLR4-MyD88-NF-kappaB axis provides a novel link between proinflammatory and profibrogenic signals...
  28. ncbi Non-Smad signaling pathways
    Yabing Mu
    Medical Biosciences, Umea University, SE 901 85 Umea, Sweden
    Cell Tissue Res 347:11-20. 2012
    ..In this review, we discuss recent findings in the field of TGFβ-induced responses by non-Smad signaling pathways...
  29. pmc A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism
    Janine L Coombes
    Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
    J Exp Med 204:1757-64. 2007
    ..These results newly identify RA as a cofactor in T reg cell generation, providing a mechanism via which functionally specialized gut-associated lymphoid tissue DCs can extend the repertoire of T reg cells focused on the intestine...
  30. ncbi Transforming growth factor beta in tissue fibrosis
    W A Border
    Division of Nephrology, University of Utah School of Medicine, Salt Lake City 84132
    N Engl J Med 331:1286-92. 1994
  31. ncbi Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells
    Eva V Acosta-Rodriguez
    Institute for Research in Biomedicine, CH 6500 Bellinzona, Switzerland
    Nat Immunol 8:942-9. 2007
    ....
  32. pmc MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA
    William Kong
    Departments of Molecular Oncology, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, SRB3, Tampa, FL 33612, USA
    Mol Cell Biol 28:6773-84. 2008
    b>Transforming growth factor beta (TGF-beta) signaling facilitates metastasis in advanced malignancy...
  33. pmc Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF
    V A Fadok
    Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA
    J Clin Invest 101:890-8. 1998
    ..Therefore, it is likely that resolution of inflammation depends not only on the removal of apoptotic cells but on active suppression of inflammatory mediator production. Disorders in either could result in chronic inflammatory diseases...
  34. pmc Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors
    Marie Jose Goumans
    Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    EMBO J 21:1743-53. 2002
    ..Our results suggest that TGF-beta regulates the activation state of the endothelium via a fine balance between ALK5 and ALK1 signalling...
  35. ncbi TGFbeta signalling: a complex web in cancer progression
    Hiroaki Ikushima
    Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo 113 0033, Japan
    Nat Rev Cancer 10:415-24. 2010
    ....
  36. ncbi Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer
    Peter M Siegel
    Cancer Biology and Genetics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Nat Rev Cancer 3:807-21. 2003
  37. ncbi Mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition
    Carl Henrik Heldin
    Ludwig Institute for Cancer Research, Uppsala University, BMC, Uppsala, Sweden
    Curr Opin Cell Biol 21:166-76. 2009
    ..The aim of this review is to summarize some of the recent findings on the mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition...
  38. pmc Double muscling in cattle due to mutations in the myostatin gene
    A C McPherron
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 94:12457-61. 1997
    Myostatin (GDF-8) is a member of the transforming growth factor beta superfamily of secreted growth and differentiation factors that is essential for proper regulation of skeletal muscle mass in mice...
  39. ncbi A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses
    Elisabetta Volpe
    Institut National de la Sante et de la Recherche Medicale U653, Paris F 75248, France
    Nat Immunol 9:650-7. 2008
    ..Our results shed new light on the regulation of human T(H)-17 differentiation and provide a framework for the global analysis of T helper responses...
  40. ncbi Specificity and versatility in tgf-beta signaling through Smads
    Xin Hua Feng
    Department of Molecular and Cellular Biology, Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas 77030, USA
    Annu Rev Cell Dev Biol 21:659-93. 2005
    ..We review the molecular basis for the specificity and versatility of signaling by the many ligands through this conceptually simple signal transduction mechanism...
  41. ncbi Roles of TGFbeta in metastasis
    David Padua
    Cancer Biology and Genetics Program, and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 116, New York, NY 10065, USA
    Cell Res 19:89-102. 2009
    ..The development of TGFbeta inhibitors for clinical use will require a deeper understanding of TGFbeta signaling, its consequences, and the contexts in which it acts...
  42. ncbi Transforming growth factor-beta induces development of the T(H)17 lineage
    Paul R Mangan
    Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294 2170, USA
    Nature 441:231-4. 2006
    ..The action of TGF-beta on naive T cells is antagonized by interferon-gamma and IL-4, thus providing a mechanism for divergence of the T(H)1, T(H)2 and T(H)17 lineages...
  43. ncbi A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle
    L Grobet
    Department of Genetics, Faculty of Veterinary Medicine, University of Liege, Belgium
    Nat Genet 17:71-4. 1997
    ..We report an 11-bp deletion in the coding sequence for the bioactive carboxy-terminal domain of the protein causing the muscular hypertrophy observed in Belgian Blue cattle...
  44. ncbi Non-Smad TGF-beta signals
    Aristidis Moustakas
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, Box 595, SE 751 24 Uppsala, Sweden
    J Cell Sci 118:3573-84. 2005
    ..been firmly established that Smad pathways are central mediators of signals from the receptors for transforming growth factor beta (TGF-beta) superfamily members to the nucleus...
  45. pmc Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis
    Li Yang
    Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Cancer Cell 13:23-35. 2008
    ..Together, these data indicate that Gr-1+CD11b+ cells contribute to TGFbeta-mediated metastasis through enhancing tumor cell invasion and metastasis...
  46. ncbi E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer
    Fabio Petrocca
    Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Ohio State University, 460 West 12th Avenue, Columbus, OH 43210, USA
    Cancer Cell 13:272-86. 2008
    ..Together, these results suggest that the miR-106b-25 cluster is involved in E2F1 posttranscriptional regulation and may play a key role in the development of TGFbeta resistance in gastric cancer...
  47. pmc Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease
    M M Shull
    Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Ohio 45267 0524
    Nature 359:693-9. 1992
    ..TGF-beta 1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions...
  48. ncbi Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms
    Ming O Li
    Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Immunity 25:455-71. 2006
    ..This study reveals pleiotropic functions of TGF-beta signaling in T cells that may ensure a diverse and self-tolerant T cell repertoire in vivo...
  49. pmc Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis
    Q Yu
    Molecular Pathology Unit, Massachusetts General Hospital, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02129 USA
    Genes Dev 14:163-76. 2000
    ..These observations suggest that coordinated CD44, MMP-9, and TGF-beta function may provide a physiological mechanism of tissue remodeling that can be adopted by malignant cells to promote tumor growth and invasion...
  50. ncbi Tgf-beta superfamily signaling in embryonic development and homeostasis
    Mary Y Wu
    Laboratory of Developmental Signalling, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Dev Cell 16:329-43. 2009
    ..Finally, we discuss how these ligands act as morphogens, how their activity and signaling range is regulated, and how they interact with other signaling pathways to achieve their specific and varied functional roles...
  51. ncbi Mutations in myostatin (GDF8) in double-muscled Belgian Blue and Piedmontese cattle
    R Kambadur
    AgResearch, Ruakura, Hamilton, New Zealand
    Genome Res 7:910-6. 1997
    ..It therefore appears likely that the mh allele in these breeds involves mutation within the myostatin gene and that myostatin is a negative regulator of muscle growth in cattle as well as mice...
  52. pmc Transcriptional control by the TGF-beta/Smad signaling system
    J Massague
    Cell Biology Program and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    EMBO J 19:1745-54. 2000
  53. ncbi New insights into TGF-beta-Smad signalling
    Peter Ten Dijke
    Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Trends Biochem Sci 29:265-73. 2004
    b>Transforming growth factor beta (TGF-beta) initiates its diverse cellular responses by binding to and activating specific cell surface receptors that have intrinsic serine/threonine kinase activity...
  54. ncbi TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells
    Marc Veldhoen
    Division of Molecular Immunology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    Immunity 24:179-89. 2006
    ..Our data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells...
  55. pmc Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis
    Brigham C Willis
    Department of Anesthesiology Critical Care Medicine, Childrens Hospital Los Angeles, California, USA
    Am J Pathol 166:1321-32. 2005
    ..These results suggest that AECs undergo EMT when chronically exposed to TGF-beta1, raising the possibility that epithelial cells may serve as a novel source of myofibroblasts in IPF...
  56. ncbi TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease
    Brigham C Willis
    Heart and Lung Institute, St Joseph s Hospital and Medical Center, Phoenix, Arizona, USA
    Am J Physiol Lung Cell Mol Physiol 293:L525-34. 2007
    ....
  57. ncbi Transforming growth factor-beta regulation of immune responses
    Ming O Li
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Annu Rev Immunol 24:99-146. 2006
    ..This review highlights the findings that have advanced our understanding of TGF-beta in the immune system and in disease...
  58. ncbi DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1
    S A Hahn
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Science 271:350-3. 1996
    ..1. These results identify DPC4 as a candidate tumor suppressor gene whose inactivation may play a role in pancreatic and possibly other human cancers...
  59. pmc SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression
    Zhihu Ding
    Belfer Institute for Applied Cancer Science, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 470:269-73. 2011
    ..This model-informed progression analysis, together with genetic, functional and translational studies, establishes SMAD4 as a key regulator of PCA progression in mice and humans...
  60. ncbi Signal transduction by the TGF-beta superfamily
    Liliana Attisano
    Department of Anatomy and Cell Biology, University of Toronto, Toronto M5S 1A8, Canada
    Science 296:1646-7. 2002
    ..Current research efforts investigating the contribution of SMAD-independent pathways promise to reveal advances to enhance our understanding of the signaling cascade...
  61. ncbi Renal fibrosis: new insights into the pathogenesis and therapeutics
    Youhua Liu
    Division of Cellular and Molecular Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Kidney Int 69:213-7. 2006
    ..This mini-review attempts to highlight the recent progress in our understanding of the cellular and molecular pathways leading to renal fibrosis, and discusses the challenges and opportunities in developing therapeutic strategies...
  62. ncbi Comprehensive analysis of the independent effect of twist and snail in promoting metastasis of hepatocellular carcinoma
    Muh Hwa Yang
    Institutes of Clinical Medicine, National Yang Ming University, Taipei, Taiwan
    Hepatology 50:1464-74. 2009
    ..Twist and Snail were independently regulated, but exerted an additive inhibitory effect to suppress E-cadherin transcription...
  63. ncbi TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility
    Bernhard Schmierer
    Developmental Signalling Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London, WC2A 3PX, UK
    Nat Rev Mol Cell Biol 8:970-82. 2007
    ..How are these quantitative aspects of the extracellular signal regulated? How are they then sensed and interpreted, and how do they affect responses?..
  64. pmc Signaling cross-talk between TGF-beta/BMP and other pathways
    Xing Guo
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Cell Res 19:71-88. 2009
    ....
  65. pmc Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways
    Claudio Alarcon
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Cell 139:757-69. 2009
    ..Thus, nuclear CDK8/9 drive a cycle of Smad utilization and disposal that is an integral part of canonical BMP and TGF-beta pathways...
  66. ncbi Myostatin mutation associated with gross muscle hypertrophy in a child
    Markus Schuelke
    Department of Neuropediatrics, Charite, University Medical Center Berlin, Berlin, Germany
    N Engl J Med 350:2682-8. 2004
  67. pmc Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome
    Jennifer P Habashi
    Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Science 312:117-21. 2006
    ....
  68. ncbi Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction
    K Yamaguchi
    Department of Molecular Biology, Faculty of Science, Nagoya University, Japan
    Science 270:2008-11. 1995
    ..Furthermore, kinase activity of TAK1 was stimulated in response to TGF-beta and bone morphogenetic protein. These results suggest that TAK1 functions as a mediator in the signaling pathway of TGF-beta superfamily members...
  69. ncbi Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer
    E Y Woo
    Department of Surgery, Abramson Family Cancer Research Institute, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA
    Cancer Res 61:4766-72. 2001
    ..These observations provide evidence for the contribution of regulatory T cells to immune dysfunction in cancer patients...
  70. ncbi The dynamic roles of TGF-β in cancer
    Erik Meulmeester
    Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Postbus 9600, 2300 RC, Leiden, The Netherlands
    J Pathol 223:205-18. 2011
    ..However, considering the important role of TGF-β in cardiovascular and many other tissues, careful screening of patients is warranted to minimize unwanted on-target side effects...
  71. ncbi The specificities of small molecule inhibitors of the TGFß and BMP pathways
    Janis Vogt
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK
    Cell Signal 23:1831-42. 2011
    ..Our observations have highlighted the need for caution when using these small molecule inhibitors to assess the physiological roles of BMP and TGFß pathways...
  72. ncbi Alterations in components of the TGF-beta superfamily signaling pathways in human cancer
    Laurence Levy
    Laboratory of Developmental Signalling, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Cytokine Growth Factor Rev 17:41-58. 2006
    ....
  73. ncbi BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury
    Michael Zeisberg
    Center for Matrix Biology, Gastroenterology and Renal Divisions, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Nat Med 9:964-8. 2003
    ..Collectively, these results provide evidence of cross talk between BMP-7 and TGF-beta1 in the regulation of EMT in health and disease...
  74. ncbi A multigenic program mediating breast cancer metastasis to bone
    Yibin Kang
    Cell Biology Program and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Cancer Cell 3:537-49. 2003
    ....
  75. ncbi Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor beta signaling
    Fabio Petrocca
    Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA
    Cancer Res 68:8191-4. 2008
    Inactivation of the transforming growth factor beta (TGFbeta) tumor suppressor pathway is a main step in the development of a variety of human tumors...
  76. pmc Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology
    Terrence Town
    Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, Connecticut 06520 8011, USA
    Nat Med 14:681-7. 2008
    ..Taken together, our results suggest that blockade of TGF-beta-Smad2/3 signaling in peripheral macrophages represents a new therapeutic target for Alzheimer's disease...
  77. pmc NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression
    Margit A Huber
    Department of Physiological Chemistry, Ulm University, Albert Einstein Allee 11, D 89081 Ulm, Germany
    J Clin Invest 114:569-81. 2004
    ....
  78. ncbi The logic of TGFbeta signaling
    Joan Massague
    Cancer Biology and Genetics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, P O Box 116, 1275 York Avenue, New York, NY 10021, USA
    FEBS Lett 580:2811-20. 2006
    ..The deconstruction of one of these responses - the cell cycle arrest response - into its elemental molecular parts has shed light into the mechanisms used by tumors to evade surveillance and cause metastasis...
  79. pmc TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta
    Motozo Yamashita
    Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Cell 31:918-24. 2008
    ..Our results indicate that TGF-beta activates JNK and p38 through a mechanism similar to that operating in the interleukin-1beta/Toll-like receptor pathway...
  80. pmc MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors
    Mitsuo Kato
    Gonda Diabetes Center, Division of Molecular Biology, Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA
    Proc Natl Acad Sci U S A 104:3432-7. 2007
    ..These results uncover a role for miRs in the kidney and DN in controlling TGF-beta-induced Col1a2 expression by down-regulating E-box repressors...
  81. pmc Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death
    A B Kulkarni
    Molecular Medical Genetics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 90:770-4. 1993
    To delineate specific developmental roles of transforming growth factor beta 1 (TGF-beta 1) we have disrupted its cognate gene in mouse embryonic stem cells by homologous recombination to generate TGF-beta 1 null mice...
  82. pmc Targeting of SMAD5 links microRNA-155 to the TGF-beta pathway and lymphomagenesis
    Deepak Rai
    Division of Hematology and Medical Oncology, Department of Medicine, University of Texas Health Science Center, San Antonio, TX 78229, USA
    Proc Natl Acad Sci U S A 107:3111-6. 2010
    ..Together, our data helped explain miR-155 function, highlighted a hitherto unappreciated role of SMAD5 in lymphoma biology, and defined a unique mechanism used by cancer cells to escape TGF-beta's growth-inhibitory effects...
  83. pmc Lessons on the pathogenesis of aneurysm from heritable conditions
    Mark E Lindsay
    Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205 1832, USA
    Nature 473:308-16. 2011
    ..The modelling of single-gene heritable aneurysm disorders in mice has shown unexpected involvement of the transforming growth factor-β cytokine pathway in aortic aneurysm, highlighting the potential for new therapeutic strategies...
  84. ncbi Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition
    Michael Zeisberg
    Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachussetts 02215, USA
    J Biol Chem 282:23337-47. 2007
    ..Furthermore, our findings suggest that EMT is a promising therapeutic target for the attenuation of liver fibrosis...
  85. pmc The two faces of transforming growth factor beta in carcinogenesis
    Anita B Roberts
    Laboratory of Cell Regulation and Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 5055, USA
    Proc Natl Acad Sci U S A 100:8621-3. 2003
  86. pmc TGF-beta1 induces human alveolar epithelial to mesenchymal cell transition (EMT)
    Hidenori Kasai
    Teijin Biomedical Laboratory, Medical Research Council Technology, 1 3 Burtonhole Lane, London, NW7 1AD, UK
    Respir Res 6:56. 2005
    ..We examined whether the potent fibrogenic cytokine TGF-beta1 could induce epithelial mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-beta1-mediated EMT...
  87. pmc TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function
    Liang Zhou
    The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA
    Nature 453:236-40. 2008
    ..Therefore, the decision of antigen-stimulated cells to differentiate into either T(H)17 or T(reg) cells depends on the cytokine-regulated balance of RORgammat and Foxp3...
  88. ncbi Recruitment of TIF1γ to chromatin via its PHD finger-bromodomain activates its ubiquitin ligase and transcriptional repressor activities
    Eleonora Agricola
    Laboratory of Developmental Signalling, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Mol Cell 43:85-96. 2011
    ..We propose a model of TIF1γ activity in which it dictates the residence time of activated Smad complexes at promoters of TGF-β superfamily target genes...
  89. ncbi FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination
    Sirio Dupont
    Department of Histology, Microbiology, and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35131 Padua, Italy
    Cell 136:123-35. 2009
    ..This defines a regulative ubiquitination step controlling Smads that is parallel to those impinging on R-Smad phosphorylation...
  90. 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
    ..The gene encoding p15 is located on chromosome 9 adjacent to the p16 gene at a frequent site of chromosomal abnormality in human tumours (9p21)...
  91. ncbi Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFbeta/ALK5 signaling
    Marie Jose Goumans
    Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
    Mol Cell 12:817-28. 2003
    ..TGFbeta type II receptor is also required for ALK1 activation by TGFbeta. Interestingly, ALK1 not only induces a biological response opposite to that of ALK5 but also directly antagonizes ALK5/Smad signaling...
  92. pmc Cellular and molecular basis for the regulation of inflammation by TGF-beta
    Akihiko Yoshimura
    Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    J Biochem 147:781-92. 2010
    ..Interaction between TGF-beta and other cytokine signaling is important in establishing the balance of immunity and tolerance...
  93. pmc A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition
    Theresa Vincent
    Ludwig Institute for Cancer Research, Stockholm Branch, 17177 Stockholm, Sweden
    Nat Cell Biol 11:943-50. 2009
    ..We propose that activation of a SNAIL1-SMAD3/4 transcriptional complex represents a mechanism of gene repression during EMT...
  94. pmc Phospho-control of TGF-beta superfamily signaling
    Katharine H Wrighton
    Michael E DeBakey Department of Surgery, Department of Molecular and Cellular Biology and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
    Cell Res 19:8-20. 2009
    ..This article illustrates the essential roles of reversible phosphorylation in controlling the strength and duration of TGF-beta signaling and the ensuing physiological responses...
  95. pmc TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression
    Li Yang
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20876, USA
    Trends Immunol 31:220-7. 2010
    b>Transforming growth factor beta (TGF-beta) plays an important role in tumor initiation and progression, functioning as both a suppressor and a promoter. The mechanisms underlying this dual role of TGF-beta remain unclear...
  96. pmc Inactivation of smad-transforming growth factor beta signaling by Ca(2+)-calmodulin-dependent protein kinase II
    S J Wicks
    Department of Cancer Medicine, Division of Medicine, Imperial College School of Medicine, Hammersmith Campus, London W12 ONN, United Kingdom
    Mol Cell Biol 20:8103-11. 2000
    Members of the transforming growth factor beta (TGF-beta) family transduce signals through Smad proteins...
  97. pmc Transforming growth factor beta engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab
    Shizhen Emily Wang
    Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Mol Cell Biol 28:5605-20. 2008
    In HER2-overexpressing mammary epithelial cells, transforming growth factor beta (TGF-beta) activated phosphatidylinositol-3 kinase (PI3K)/Akt and enhanced survival and migration...
  98. ncbi A crucial function of PDGF in TGF-beta-mediated cancer progression of hepatocytes
    J Gotzmann
    Department of Medicine I, Division Institute of Cancer Research, Medical University of Vienna, Vienna, Austria
    Oncogene 25:3170-85. 2006
    ..In conclusion, these results provide evidence for a crucial role of PDGF in TGF-beta-mediated tumour progression of hepatocytes and suggest PDGF as a target for therapeutic intervention in liver cancer...
  99. pmc The Six1 homeoprotein induces human mammary carcinoma cells to undergo epithelial-mesenchymal transition and metastasis in mice through increasing TGF-beta signaling
    Douglas S Micalizzi
    Program in Molecular Biology, University of Colorado School of Medicine, Aurora, Colorado 80045, USA
    J Clin Invest 119:2678-90. 2009
    ..Our findings indicate that Six1, acting through TGF-beta signaling and EMT, is a powerful and global promoter of cancer metastasis...
  100. pmc Chromatin immunoprecipitation on microarray analysis of Smad2/3 binding sites reveals roles of ETS1 and TFAP2A in transforming growth factor beta signaling
    Daizo Koinuma
    Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, Koto ku, Tokyo 135 8550, Japan
    Mol Cell Biol 29:172-86. 2009
    The Smad2 and Smad3 (Smad2/3) proteins are principally involved in the transmission of transforming growth factor beta (TGF-beta) signaling from the plasma membrane to the nucleus...
  101. pmc Review of the activation of TGF-beta in immunity
    Andrew W Taylor
    Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114, USA
    J Leukoc Biol 85:29-33. 2009
    ..A mechanistic understanding of the process activating TGF-beta can lead to regulating multiple biological systems by enhancing or inhibiting TGF-beta activation...

Research Grants71

  1. BBP (Bone Morphogenetic Protein Binding Peptide) and Bone Healing
    SAMUEL SCOTT MURRAY; Fiscal Year: 2013
    ..We will also determine how the native bone protein spp24 (secreted phosphoprotein-24 kDa) inhibits BMP/TGF-b-dependent tumor cell growth. ..
  2. Radiation-Induced Osteoporosis in Women with Cancer: Mechanisms and Prevention
    Ted A Bateman; Fiscal Year: 2013
    ....
  3. Novel Biomarkers in Aortic Aneurysms and Acute Aortic Dissection
    JENNIFER E contact VAN EYK; Fiscal Year: 2010
    ..The current proposal will use proteomics techniques in an advanced animal model of aortic aneurysms and dissections to gain insight into these mechanisms and validate the findings in a large population of patients with aortic diseases. ..
  4. Engineering the Brain Immune System for Tumor Therapy
    Maria G Castro; Fiscal Year: 2013
    ..e., transforming growth factor beta. Nevertheless, experimental and clinical studies have shown that immune-therapy can effectively ..
  5. Hepatocyte Nox proteins in the pathogenesis of hepatocellular carcinoma
    Jinah Choi; Fiscal Year: 2013
    ..HCV elevated Nox4 through a fibrogenic cytokine, transforming growth factor beta 1. In addition, HCV infection is characterized by chronic, low level of inflammation...
  6. TRANSFORMING GROWTH FACTOR - BETA MEDIATES EFFECTS OF HYPOXIA IN NEWBORN LUNG
    Namasivayam Ambalavanan; Fiscal Year: 2012
    ....
  7. ATRIAL NATRIURETIC PEPTIDE AND RECEPTOR GENES IN HYPOXIA
    Yiu Fai Chen; Fiscal Year: 2010
    ..Our proposed mechanistic studies will lead to innovative and effective therapeutic approaches to this important cause of morbidity and mortality in the American population. ..
  8. Mechanisms of cancer initiation by TRIM32
    Molly F Kulesz-Martin; Fiscal Year: 2012
    ..abstract_text> ..
  9. Virus interference with Toll like Receptor Response on Dendritic Cells
    Elina I Zuniga; Fiscal Year: 2010
    ..Furthermore, I will investigate the role of the infectious environment, particularly transforming growth factor beta signaling on DCs, on DC dysfunction during LCMV infection and its impact on primary and secondary ..
  10. GROWTH CONTROL OF NORMAL AND CIRRHOTIC HEPATOCYTES
    Kevin E Behrns; Fiscal Year: 2010
    ..that murine cirrhotic hepatocytes exhibited markedly decreased apoptosis after treatment with transforming growth factor beta (TGFbeta), tumor necrosis factor alpha (TNFalpha), and ultraviolet radiation...
  11. Innate immunity in dermal fibrosis and systemic sclerosis
    ROBERT A LAFYATIS; Fiscal Year: 2013
    ....
  12. TGF-Beta in Intimal Hyperplasia after Vascular Bypass
    K Craig Kent; Fiscal Year: 2013
    ..The long-term goal is to develop specific therapies that prevent or halt the progression of arterial restenosis, thus reducing morbidity and mortality for thousands of individuals each year. ..
  13. Cellular Senescence and Glaucoma
    Pedro Gonzalez; Fiscal Year: 2011
    ..production of ROS and inflammatory mediators;and 3) To test whether miR-29 is an inhibitor the transforming growth factor beta 1 and Wnt pathways, and that downregulation of this miRNA by chronic oxidative stress leads to ..
  14. REGULATION OF STROMAL WOUND HEALING BY GROWTH FACTORS
    GREGORY SCOTT SCHULTZ; Fiscal Year: 2012
    ..research identified two growth factors that are the major regulators of scar formation in the cornea, transforming growth factor beta (TGFb), and its downstream mediator, connective tissue growth factor (CTGF)...
  15. Individual Predoctoral Dental Scientist Fellowship
    Angela Gullard; Fiscal Year: 2013
    ..This research will elucidate the role of tooth/bone matrix material properties in oral and skeletal health and disease. ..
  16. Epithelial JNK-TGFb1 Signaling Axis in Airway Remodeling
    Yvonne M W Janssen-Heininger; Fiscal Year: 2013
    ..The pro-fibrotic cytokine, transforming growth factor beta-1 (TGF-[unreadable]1) plays a cardinal role in fibrogenesis...
  17. Development of a Topical Choroid Plexus Factor Product to Accelerate Wound Healin
    CHRISTOPHER GORDON THANOS; Fiscal Year: 2011
    ..endothelial growth factor, platelet derived growth factor, connective tissue growth factor, and transforming growth factor beta are among hundreds of potentially regenerative factors secreted by the CP...
  18. Using Genetics For Early Phenotyping &Prevention of Hypertrophic Cardiomyopathy
    Christine E Seidman; Fiscal Year: 2013
    ..Early treatment can be targeted to at-risk, genetically susceptible individuals to offset the consequences of pathogenic mutations and prevent disease progression. ..
  19. MOLECULAR MANIPULATION TO ENHANCE ANTI-MYELOMA RESPONSE
    Nikhil C Munshi; Fiscal Year: 2013
    ..The proposed studies will identify the mechanism of immune suppression in myeloma, develop methods to improve immune function and develop peptide-based vaccination strategies to preclinical rational for their clinical application. ..
  20. Systems analysis of TGFbeta signaling and SnoN function in liver
    Kunxin Luo; Fiscal Year: 2013
    ..The long-term goal of this project is to understand how proper levels of TGF2 signaling activity are maintained and regulated in normal tissues and primary cells using a system biology approach. ..
  21. Transforming Growth Factor-beta Signaling Pathways in Thoracic Aortic Aneurysms
    Jeffrey A Jones; Fiscal Year: 2013
    ....
  22. Control of Colonic Inflammation and Tumor Growth by TGFBeta and Dietary Vitamin D
    Lillian Maggio-Price; Fiscal Year: 2012
    ..The detailed understanding of dietary effects and molecular mechanisms will permit more targeted and effective therapies for treatment of these diseases. ..
  23. Molecular Biology of Marfan Syndrome
    Harry C Dietz; Fiscal Year: 2013
    ..These studies have the strong potential to unveil novel therapeutic targets and strategies for MFS and perhaps more common presentations of aneurysm. ..
  24. Human Milk Factor Protection in Neonatal Necrotizing Enterocolitis
    Sheng Ru Shiou; Fiscal Year: 2012
    ..This proposal will investigate how Epo and TGF-b protect immature intestine, in order to develop a treatment to prevent or ameliorate NEC in vulnerable infants. ..
  25. Angiotensin-II, Hypothalamic Inflammation and Neurogenic Hypertension
    ANNETTE DIANE DE KLOET; Fiscal Year: 2012
    ..approaches in mice will be used to determine the role of interactions between PVN AT1a, transforming growth factor beta and inflammation in the regulation of cardiovascular function during elevated Ang-II...
  26. Retinoids and Hyperoxic Lung Injury
    Masheika L James; Fiscal Year: 2012
    ..abstract_text> ..
  27. Individual Predoctoral Dental Scientist Fellowship
    MELISSA ANNE TALBERT; Fiscal Year: 2011
    ..b>Transforming growth factor beta (TGF-[unreadable]) is a key factor driving fibrotic responses and impedes osteoblast differentiation...
  28. EFFECT OF ETHANOL ON CELL PROLIFERATION
    Frank A Middleton; Fiscal Year: 2013
    ..In concert, the novel Aims will use three complementary models to gain critical insight into mechanisms defining cell proliferation and fate and the effects of ethanol on these critical factors. ..
  29. microRNA regulatory function in Leiomyoma growth
    Xiaoping Luo; Fiscal Year: 2010
    ..b>Transforming growth factor beta (TGF-[unreadable]) is a multifunction cytokine whose overexpression serves as a key regulator of ..
  30. Myostatin Regulation of Skeletal Muscle Energy Metabolism
    SUZANNE PORSZASZ-REISZ; Fiscal Year: 2013
    ..Myostatin (Mst) is a secreted protein that belongs to the transforming growth factor beta (TGF-2) family;it regulates skeletal muscle mass, modulates transcription of muscle-specific genes, ..
  31. Regulatory Mechanisms of Implant-Induced Osteolysis
    Yousef Abu-Amer; Fiscal Year: 2013
    ..In our recent work, we found that PMMA particles directly activate the upstream transforming growth factor beta activated kinase-1 (TAK1) which is a key regulator of signal transduction cascades leading to ..
  32. Transforming Growth Factor-Beta Signal Transduction
    Joan Massague; Fiscal Year: 2013
    ..Building on this progress, we will investigate the connectivity and regulation of TGF-beta and BMP pathways with other major regulators of cell behavior in the normal and the malignant state. ..
  33. HORMONAL REGULATION OF ETHANOL METABOLISM
    Esteban Mezey; Fiscal Year: 2011
    ..b>Transforming growth factor beta (TGFbeta) is a principal stimulator of fibrogenesis...
  34. Mesenchymal Regulation of Jaw Bone Length
    Erin L Ealba; Fiscal Year: 2013
    ..We are hopeful that our research will provide a foundation for biologically based, non-surgical methods to remedy a variety of clinical skeletal conditions. ..
  35. Transforming Growth Factor-Beta (TGF-b) Signaling in Aged Skin
    Taihao Quan; Fiscal Year: 2013
    ..This hypothesis is novel because it focuses on the importance of the extracellular matrix, rather than inherent cellular deficits, as a driving force for the aging process in humans. ..
  36. Age-Dependent Mechanisms in Thoracic Aortic Aneurysms
    John S Ikonomidis; Fiscal Year: 2013
    ....
  37. Host MMP-mediated regulation of the vicious cycle of prostate to bone metastases
    Conor C Lynch; Fiscal Year: 2013
    ..namely parathyroid related peptide (PTHrP), receptor activator of nuclear kappa B ligand (RANKL) and transforming growth factor beta (TGF[unreadable])...
  38. Mesenchymal Cell Fate Determination by Extracellular Matrix Stiffness
    Jeffrey C Horowitz; Fiscal Year: 2013
    ..of the myofibroblast fate regulation, however, have focused on the effects of soluble mediators (transforming growth factor beta-1 and endothelin-1), using rigid plastic substrates with supra-physiologic stiffness...
  39. Epigenetic profiling of human alveolar epithelial cells in health and disease
    Ite A Laird-Offringa; Fiscal Year: 2013
    ..AEC have been shown to undergo EMT in vivo in response to transforming growth factor beta (TGF-[unreadable]), giving rise to (myo)fibroblasts...
  40. Cell Specific Responses to TNF-alpha in Lung Fibrosis
    Gloria Pryhuber; Fiscal Year: 2009
    ..Lung disease caused by inhaled dust is a significant world wide health problem. This proposal will identify new targets for therapy of these chronic and often deadly diseases with reduced side effects. ..
  41. Improved Drug Delivery to Tumors Using Novel Tissue Perfusion Approaches
    HEIKE ELIZABETH DALDRUP-LINK; Fiscal Year: 2012
    ..Whereas transforming growth factor beta 1 (TGF?1) restricts normal vascular permeability, inhibition of the type I TGF??receptor Alk5 ..
  42. TGFBM2 in Development and Disease
    Rosemary J Akhurst; Fiscal Year: 2012
    The transforming growth factor beta signaling pathway is strongly implicated in many common diseases considered to be multifactorial in etiology, including cancer, cardiovascular disease, asthma, fibrosis and inflammation...
  43. Role of Transforming Growth Factor-beta in Neonatal Necrotizing Enterocolitis
    Akhil Maheshwari; Fiscal Year: 2013
    ....
  44. Molecular Mechanisms of the Increased Cardiovascular Risk in Rheumatoid Arthritis
    MARIO CESAR RICO; Fiscal Year: 2013
    ..The alpha granules of platelets contain thrombospondin-1 (TSP1) and transforming growth factor beta (TGFb), which are anti-angiogenic and anti-inflammatory molecules, respectively...
  45. TGF-BETA REGULATION OF INTESTINAL EPITHELIAL CELLS
    John Barnard; Fiscal Year: 2009
    ..Over the past decade, we have studied the autocrine growth inhibitory factor, transforming growth factor beta(TGFbeta), in normal and aberrant intestinal epithelial growth...
  46. MCP5 as key mediator of TGFbeta signaling in joint maintenance and osteoarthritis
    Lara Longobardi; Fiscal Year: 2013
    ..Our studies will provide critical insights on joint development homeostasis and OA pathophysiology. ..
  47. Mechanisms of Right Ventricular Dysfunction in PAH
    DAVID ALAN KASS; Fiscal Year: 2013
    ....
  48. Role of TGIF in Wnt-Induced Bone Formation
    Azeddine Atfi; Fiscal Year: 2013
    ..The homeodomain protein TGIF functions as a transcriptional corepressor in the transforming growth factor beta (TGF-[unreadable]) signaling pathway, which is known to restrict bone formation...
  49. Mechanisms of proteasomal regulation of fibrosis
    Manu Jain; Fiscal Year: 2013
    ..Targeting this protein would represent a new and novel therapeutic strategy for the treatment of Veterans with lung fibrosis. ..
  50. The role of Spry2 in regulation of bone formation
    Ophir D Klein; Fiscal Year: 2012
    ..Knowledge about the molecular pathways controlling bone formation and mineralization is thus of major clinical importance. The experiments in this R03 application will enhance our understanding of these pathways. ..
  51. Effect of PPAR?? Ligands on Alcohol-Induced Alveolar Macrophage Dysfunction
    Samantha M Yeligar; Fiscal Year: 2011
    ..ingestion reduces peroxisome proliferator- activated receptor gamma (PPARg) levels and increases transforming growth factor beta-1 (TGF21) expression, leading to alveolar macrophage (AM) alternative activation and dysfunction...
  52. TGF BETA RECEPTOR AND TUMOR PROGRESSION
    Luzhe Sun; Fiscal Year: 2012
    ..The long-term goal of our competitive renewal application is to determine whether and how transforming growth factor beta (TGF?) signaling pathway can be targeted for the development of novel therapeutic approaches to ..
  53. T cell activation requirement in autoimmune demyelination
    Michael K Racke; Fiscal Year: 2010
    ..In addition, we will examine the production of IL-17-producing T cells from patients with multiple sclerosis and determine whether the current immunomodulatory therapies affect secretion of this cytokine. ..
  54. Dysregulation of TGF Beta Action Pancreatic Cancer
    Murray Korc; Fiscal Year: 2012
    Pancreatic ductal adenocarcinomas (PDACs) overexpress all three transforming growth factor beta (TGF-2) isoforms and inhibitory Smad7, and frequently harbor Kras mutations...
  55. Pregnancy specific glycoprotein 1 activates transforming growth factor beta
    Gabriela S Dveksler; Fiscal Year: 2013
    ..This project will define the mechanism of action o PSG1 and address a possible novel mechanism of TGF-b1 and TGF-b2 activation. ..
  56. TGF-beta and Common gamma-Chain Cytokine Crosstalk in T Cell Regulation
    Ming Li; Fiscal Year: 2013
    ..Successful completion of the projects outlined in this proposal will generate mechanistic insights into the crosstalk between TGF-beta and the common gamma-chain cytokines in T cell regulation. ..
  57. Targeted delivery of TGFbeta blockade to diseased glomeruli
    Yufeng Huang; Fiscal Year: 2010
    ....
  58. Mechanisms of Renal Protection with Volatile Anesthetics
    H Thomas Lee; Fiscal Year: 2013
    ..As such, our proposal may identify novel therapeutic targets (e.g., IL-11) and novel therapeutics (polyethylene glycol-conjugated IL-11) to reduce complications of AKI and lead to a radical reduction in mortality and morbidity. ..
  59. TGFb Modulation: Therapeutic Targeting for COPD-Emphysema
    Enid R Neptune; Fiscal Year: 2012
    ..In the current proposal, we perform a detailed evaluation of the TGFb pathway as a rational target for COPD treatment utilizing human materials, animal model systems and candidate therapeutic agents. ..
  60. Mesenchymal Regulation of Osteogenesis
    Richard A Schneider; Fiscal Year: 2013
    ..The goal of this project is to identify genes and embryonic events that control bone formation. ..
  61. Strategies for early treatment of bone metastases
    Julie A Sterling; Fiscal Year: 2013
    ..2) Evaluate the effectiveness of early bone-specific TGF-beta inhibition on bone metastases, 3) Test the effectiveness of combination therapies that inhibit both TGF-beta with Gli2 on bone metastases. ..
  62. TGF-beta Mediated Inflammatory Signaling: a Critical Role in Epileptogenesis
    Daniela Kaufer; Fiscal Year: 2012
    ..Since brain insults are one of the primary causes of disability with no means of prevention as of yet, this proposal represents an important advancement toward resolving this unmet medical need. ..
  63. Autologous TGF-B-Modified HSC for Repair of Vasodegenerative Diabetic Retinopathy
    STEPHEN BARTELMEZ; Fiscal Year: 2009
    ..If this treatment proves to be safe and effective, it will be the first "cure" for diabetic retinopathy. ..
  64. IMMUNE MONITORING OF ANTIGEN SPECIFIC THERAPY
    David Hafler; Fiscal Year: 2000
    ....
  65. BREAST CANCER METASTASES TO BONE--ROLE OF PTHRP & TGFB
    Theresa Guise; Fiscal Year: 2000
    ..Combinations of bisphosphonates with factor-specific therapy will be studied for synergistic effects. ..
  66. ASTROCYTE-NEURON INTERACTIONS AND GNRH NEURONAL FUNCTION
    Darrell Brann; Fiscal Year: 2005
    ....
  67. HIGH MOLECULAR WEIGHT TRANSFORMING GROWTH FACTOR BETA
    SAMUEL NEWCOM; Fiscal Year: 1992
    ....
  68. Kidney Damage in Murine Lupus
    Ram Singh; Fiscal Year: 2006
    ..Several reports and our preliminary data suggest a link between decreases in T cell production of transforming growth factor beta (TGFbeta) with autoantibody production, and increases in renal TGFbeta expression with the ..
  69. LIGAND BINDING DOMAINS OF TGF BETA RECEPTOR
    ANDRZEJ KREZEL; Fiscal Year: 2000
    ..This application's objective is the structural explanation of the specificity of the transforming growth factor beta (TGFbeta) binding to the TGFbeta receptors (TbetaR)...
  70. LUNG CANCER--ROLE OF PTHRP AND REGULATION BY TGFBETA
    Sarah Tannehill Gregg; Fiscal Year: 2005
    ....
  71. Studies of Pancreatic TGFBeta-Mediated Signaling
    Diane Simeone; Fiscal Year: 2007
    ..The long term goal of this project is to gain a detailed understanding of TGF signaling mechanisms in the pancreas that may be of benefit in the treatment and/or prevention of human pancreatic disease. ..