tissue inhibitor of metalloproteinases

Summary

Summary: A family of secreted proteins (TIMP-1; TIMP-2; and TIMP-3) that play a crucial role in regulating the activity of the secreted METALLOENDOPEPTIDASES; (COLLAGENASES; stromelysins; GELATINASES). Of the three characterized, only TIMP-1 and TIMP-2 appear to have related primary structures and inhibitory properties. They influence the activation of the prometalloproteinase and act to modulate proteolysis of extracellular matrix, notably during tissue remodeling and inflammatory processes. On certain cell types, they can exhibit growth factor-like activity, and they can inhibit the tumorigenic and metastatic phenotype in cancer cells. (Pharmacol Ther 1993;59:329-41)

Top Publications

  1. ncbi Structure and function of matrix metalloproteinases and TIMPs
    Hideaki Nagase
    Department of Matrix Biology, Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Road, London W6 8LH, UK
    Cardiovasc Res 69:562-73. 2006
  2. pmc The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity
    Keith Brew
    Department of Basic Science, College of Biomedical Science, Florida Atlantic University, Boca Raton, FL 33431, USA
    Biochim Biophys Acta 1803:55-71. 2010
  3. ncbi Regulation of matrix metalloproteinases: an overview
    Sajal Chakraborti
    Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India
    Mol Cell Biochem 253:269-85. 2003
  4. ncbi Metalloproteinase inhibitors: biological actions and therapeutic opportunities
    Andrew H Baker
    BHF Blood Pressure Group, Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, UK
    J Cell Sci 115:3719-27. 2002
  5. pmc Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease
    Joseph D Raffetto
    Department of Surgery, VA Boston Healthcare System, West Roxbury, MA, United States
    Biochem Pharmacol 75:346-59. 2008
  6. ncbi Tissue inhibitors of metalloproteinases: evolution, structure and function
    K Brew
    Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL 33101, USA
    Biochim Biophys Acta 1477:267-83. 2000
  7. pmc How matrix metalloproteinases regulate cell behavior
    M D Sternlicht
    Department of Anatomy, University of California, San Francisco, California 94143 0452, USA
    Annu Rev Cell Dev Biol 17:463-516. 2001
  8. pmc Metzincin proteases and their inhibitors: foes or friends in nervous system physiology?
    Santiago Rivera
    Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, Unité Mixte de Recherche 6184, Centre National de la Recherche Scientifique, Universite de la Mediterranee, 13344 Marseille, France
    J Neurosci 30:15337-57. 2010
  9. pmc Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease
    B von Lampe
    Medizinische Klinik I Gastroenterologie und Infektiologie, Klinikum Benjamin Franklin, FU Berlin, Hindenburgdamm 30, 12200 Berlin, FRG
    Gut 47:63-73. 2000
  10. ncbi Complex roles of tissue inhibitors of metalloproteinases in cancer
    Yangfu Jiang
    Department of Radiation Oncology, Long Island Jewish Medical Center, The Long Island Campus, Albert Einstein College of Medicine, New Hyde Park, New York, NY 11040, USA
    Oncogene 21:2245-52. 2002

Detail Information

Publications303 found, 100 shown here

  1. ncbi Structure and function of matrix metalloproteinases and TIMPs
    Hideaki Nagase
    Department of Matrix Biology, Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Road, London W6 8LH, UK
    Cardiovasc Res 69:562-73. 2006
    ..This review introduces the members of the MMP family and discusses their domain structure and function, proenyme activation, the mechanism of inhibition by TIMPs and their significance in physiology and pathology...
  2. pmc The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity
    Keith Brew
    Department of Basic Science, College of Biomedical Science, Florida Atlantic University, Boca Raton, FL 33431, USA
    Biochim Biophys Acta 1803:55-71. 2010
    ..A series of studies using mice with specific TIMP gene deletions has illuminated the importance of these molecules in biology and pathology...
  3. ncbi Regulation of matrix metalloproteinases: an overview
    Sajal Chakraborti
    Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India
    Mol Cell Biochem 253:269-85. 2003
    ....
  4. ncbi Metalloproteinase inhibitors: biological actions and therapeutic opportunities
    Andrew H Baker
    BHF Blood Pressure Group, Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, UK
    J Cell Sci 115:3719-27. 2002
    ....
  5. pmc Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease
    Joseph D Raffetto
    Department of Surgery, VA Boston Healthcare System, West Roxbury, MA, United States
    Biochem Pharmacol 75:346-59. 2008
    ....
  6. ncbi Tissue inhibitors of metalloproteinases: evolution, structure and function
    K Brew
    Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL 33101, USA
    Biochim Biophys Acta 1477:267-83. 2000
    ....
  7. pmc How matrix metalloproteinases regulate cell behavior
    M D Sternlicht
    Department of Anatomy, University of California, San Francisco, California 94143 0452, USA
    Annu Rev Cell Dev Biol 17:463-516. 2001
    ..Our knowledge in the field of MMP biology is rapidly expanding, yet we still do not fully understand how these enzymes regulate most processes of development, homeostasis, and disease...
  8. pmc Metzincin proteases and their inhibitors: foes or friends in nervous system physiology?
    Santiago Rivera
    Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, Unité Mixte de Recherche 6184, Centre National de la Recherche Scientifique, Universite de la Mediterranee, 13344 Marseille, France
    J Neurosci 30:15337-57. 2010
    ..The present review provides a state of the art overview of the involvement of the metzincin/TIMP system in these processes and the prospects of new therapeutic strategies based on the control of metalloproteinase activity...
  9. pmc Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease
    B von Lampe
    Medizinische Klinik I Gastroenterologie und Infektiologie, Klinikum Benjamin Franklin, FU Berlin, Hindenburgdamm 30, 12200 Berlin, FRG
    Gut 47:63-73. 2000
    ..The current study was therefore designed to determine gene expression patterns of MMPs and their tissue inhibitors (TIMPs) in single endoscopic biopsies of patients with inflammatory bowel disease (IBD)...
  10. ncbi Complex roles of tissue inhibitors of metalloproteinases in cancer
    Yangfu Jiang
    Department of Radiation Oncology, Long Island Jewish Medical Center, The Long Island Campus, Albert Einstein College of Medicine, New Hyde Park, New York, NY 11040, USA
    Oncogene 21:2245-52. 2002
    ..Elevated TIMP levels are reported in association with cancer progression and identified as poor prognostic indicators in several human tumor types. Herein, we review the complex roles of TIMPs in cancer growth and metastasis...
  11. ncbi A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2
    Jian Hua Qi
    Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
    Nat Med 9:407-15. 2003
    b>Tissue inhibitor of metalloproteinases-3 (TIMP3) is one of four members of a family of proteins that were originally classified according to their ability to inhibit matrix metalloproteinases (MMP)...
  12. ncbi Drosophila matrix metalloproteinases are required for tissue remodeling, but not embryonic development
    Andrea Page-McCaw
    Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Dev Cell 4:95-106. 2003
    ..Thus, MMPs are not required for Drosophila embryonic development, but, rather, for tissue remodeling...
  13. ncbi Matrix metalloproteinases in tumor progression: focus on basal and squamous cell skin cancer
    E Kerkela
    Department of Dermatology, Helsinki University Central Hospital, Finland
    Exp Dermatol 12:109-25. 2003
    ....
  14. ncbi Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon
    Gavin C Jones
    Rheumatology Research Unit, Addenbrooke s Hospital, Cambridge, UK
    Arthritis Rheum 54:832-42. 2006
    ....
  15. pmc Diverse patterns of cyclooxygenase-independent metalloproteinase gene regulation in human monocytes
    Buket Reel
    Bristol Heart Institute, University of Bristol, Bristol, UK
    Br J Pharmacol 163:1679-90. 2011
    ....
  16. ncbi Matrix metalloproteinases and their tissue inhibitors in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis
    I Niebroj-Dobosz
    Neuromuscular Unit, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland
    Eur J Neurol 17:226-31. 2010
    ..We investigated the expression of MMPs and tissue inhibitors of matrix metalloproteinases (TIMPs) in serum and cerebrospinal fluid (CSF) correlating the results with age, disease duration and the clinical course...
  17. ncbi Lysophosphatidic acid downregulates tissue inhibitor of metalloproteinases, which are negatively involved in lysophosphatidic acid-induced cell invasion
    S Sengupta
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
    Oncogene 26:2894-901. 2007
    ..We have found that LPA downregulates tissue inhibitor of metalloproteinases (TIMPs). TIMP2 and TIMP3 play functional role in LPA-induced invasion as negative regulators...
  18. doi Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability
    Andrew C Newby
    Bristol Heart Institute, Bristol Royal Infirmary, Bristol BS2 8HW, UK
    Arterioscler Thromb Vasc Biol 28:2108-14. 2008
    ..Moreover, recent evidence suggests that different macrophage phenotypes express characteristically different spectra of MMPs and their inhibitors. New therapies may result from targeting matrix MMP overproduction...
  19. ncbi Matrix metalloproteinases in vascular disease--a potential therapeutic target?
    Chung S Lim
    Imperial Vascular Unit, Charing Cross Campus, Imperial College, London, UK
    Curr Vasc Pharmacol 8:75-85. 2010
    ..This paper aims to summarize the scientific rationale and future perspectives in the development of effective matrix metalloproteinase (MMP) modulators in the management of patients with arterial and venous disease...
  20. ncbi Expression of MMPs and TIMPs in liver fibrosis - a systematic review with special emphasis on anti-fibrotic strategies
    Stefanie Hemmann
    Department of Medicine II, Gastroenterology, University Hospital Giessen and Marburg GmbH, Paul Meimberg Str 5, 35392 Giessen, Germany
    J Hepatol 46:955-75. 2007
    ..The methodological quality of all these publications has been critically appraised using an objective scoring system and the content has been summarized in a table...
  21. ncbi Scarless fetal wounds are associated with an increased matrix metalloproteinase-to-tissue-derived inhibitor of metalloproteinase ratio
    Catherine M Dang
    Department of Surgery, School of Medicine, University of California, Los Angeles, 90095, USA
    Plast Reconstr Surg 111:2273-85. 2003
    ..E16 scarless wounds have greater MMP relative to TIMP expression than E19 scarring wounds. This favors extracellular matrix turnover, facilitates migration of fetal cells, and promotes scarless repair...
  22. ncbi Matrix metalloproteinases promote motor axon fasciculation in the Drosophila embryo
    Crystal M Miller
    Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    Development 135:95-109. 2008
    ..These data demonstrate that MMP activity is essential for embryonic motor axon fasciculation...
  23. ncbi Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry
    Robert Visse
    Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Rd, London W6 8LH, UK
    Circ Res 92:827-39. 2003
    ....
  24. pmc 1alpha,25-dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection
    Anna Coussens
    Division of Mycobacterial Research, National Institute for Medical Research, London, UK
    Immunology 127:539-48. 2009
    ..1alpha,25(OH)(2)D(3) also induced secretion of IL-10 and PGE(2) from M. tuberculosis-infected PBMC. These findings represent a novel immunomodulatory role for 1alpha,25(OH)(2)D(3) in M. tuberculosis infection...
  25. ncbi Prognostic significance of matrix metalloproteinases-1, -2, -7 and -13 and tissue inhibitors of metalloproteinases-1, -2, -3 and -4 in colorectal cancer
    Marja Hilska
    Department of Surgery, Turku University Central Hospital, Turku, Finland
    Int J Cancer 121:714-23. 2007
    ..Different biologic behavior or different genetic development may explain the differences between colon and rectal cancers regarding the expression of MMP-2, TIMP-3 and TIMP-4...
  26. doi MMP expression and abnormal lung permeability are important determinants of outcome in IPF
    S McKeown
    Respiratory Medicine Research Group, The Queen s University of Belfast, Belfast, UK
    Eur Respir J 33:77-84. 2009
    ....
  27. ncbi Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties
    Y Okada
    Department of Pathology, School of Medicine, Kanazawa University, Japan
    J Biol Chem 267:21712-9. 1992
    ..These results indicate that MMP-9 has different activation mechanisms and substrate specificity from those of MMP-2 (72-kDa gelatinase/type IV collagenase)...
  28. ncbi Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human fetal testis and ovary
    L L Robinson
    MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, 37 Chalmers Street, University of Edinburgh, Edinburgh EH3 9ET, UK
    Mol Hum Reprod 7:641-8. 2001
    ..MMP and TIMP are likely to play a role in ECM remodelling during gonadal development and also in the cell and matrix interactions that control a range of cellular functions...
  29. pmc Matrix metalloproteinases and their tissue inhibitors in cardiac amyloidosis: relationship to structural, functional myocardial changes and to light chain amyloid deposition
    Andreia Biolo
    Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA
    Circ Heart Fail 1:249-57. 2008
    ....
  30. ncbi Dynamics of collagen, MMP and TIMP gene expression during the granulomatous, fibrotic process induced by Schistosoma mansoni eggs
    K P Singh
    Department of Immunology and Microbiology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA
    Ann Trop Med Parasitol 98:581-93. 2004
    ..These data indicate that an imbalance in MMP:TIMP expression and fibrogenic cytokine production are associated with cumulative fibrosis...
  31. ncbi Activation of a recombinant membrane type 1-matrix metalloproteinase (MT1-MMP) by furin and its interaction with tissue inhibitor of metalloproteinases (TIMP)-2
    H Sato
    Department of Molecular Virology and Oncology, Kanazawa University, Japan
    FEBS Lett 393:101-4. 1996
    ..b>Tissue inhibitor of metalloproteinases (TIMP)-2 inhibited activation of progelatinase A by forming a stable complex with activated MT1-MMP...
  32. doi Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric adenocarcinoma
    Ming Zhang
    Department of Gastroenterologic Surgery, Affiliated Tumor Hospital of Harbin Medical University, Harbin, China
    J Surg Oncol 103:243-7. 2011
    ..We examined mRNA expression for MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 in human gastric adenocarcinoma tissues, and the correlation between their expression and clinicopathological variables...
  33. doi Metalloproteases and rotator cuff disease
    Angelo Del Buono
    Department of Orthopaedic and Trauma Surgery, Campus Biomedico, University of Rome, Rome, Italy
    J Shoulder Elbow Surg 21:200-8. 2012
    ..Further studies are needed to better define the mechanism of action, and whether these new strategies are safe and effective in larger models...
  34. ncbi Role of metalloproteinases in rotator cuff tear
    Raffaele Garofalo
    Department of Orthopedic and Traumatology, F Miulli Hospital, Acquaviva delle Fonti, Bari, Italy
    Sports Med Arthrosc 19:207-12. 2011
    ..A better understanding of relationship and activity of these molecules could provide better strategies to optimize outcomes of rotator cuff therapy...
  35. ncbi Expression of matrix metalloproteinases and endogenous inhibitors within ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valves
    John S Ikonomidis
    Department of Cardiothoracic Surgical Research, Division of Cardiothoracic Surgery, Medical University of South Carolina, Ralph H Johnson Veterans Affairs Medical Center, Charleston, South Carolina 29425, USA
    J Thorac Cardiovasc Surg 133:1028-36. 2007
    ....
  36. ncbi ERK1/2 and p38 MAP kinase control MMP-2, MT1-MMP, and TIMP action and affect cell migration: a comparison between mesothelioma and mesothelial cells
    Jun Zhong
    Department of Pharmacology, The Woolcock Institute of Medical Research, University of Sydney, New South Wales, Australia
    J Cell Physiol 207:540-52. 2006
    ..Mesothelioma progression depends on an interaction with mesothelial cells that provide MT1-MMP necessary to activate pro-MMP-2 to facilitate migration through an extracellular matrix (ECM) layer...
  37. ncbi The role of IL-18 and IL-12 in the modulation of matrix metalloproteinases and their tissue inhibitors in monocytic cells
    Michal Abraham
    Neuroimmunology and Immunology Research Units, Carmel Medical Center, and Rappaport Institute for Research in the Medical Sciences, and Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
    Int Immunol 14:1449-57. 2002
    ....
  38. ncbi Matrix metalloproteases and their inhibitors are produced by overlapping populations of activated astrocytes
    E M Muir
    Department of Physiology, University of Cambridge, Cambridge CB2 3EG, UK
    Brain Res Mol Brain Res 100:103-17. 2002
    ..Conversely the MMPs produced may not be adequate to promote migration of cells and axons within the glial scar...
  39. ncbi Characterization of C-terminally truncated human tissue inhibitor of metalloproteinases-4 expressed in Pichia pastoris
    B Stratmann
    University of Bielefeld, Faculty of Chemistry, Biochemistry I, Germany
    Biol Chem 382:987-91. 2001
    ..With dissociation constants in the nanomolar range, TIMP-4 seems to be a good inhibitor for all classes of MMPs without remarkable preference for special MMPs...
  40. doi Extracellular matrix components and regulators in the airway smooth muscle in asthma
    B B Araujo
    Dept of Pathology, Sao Paulo University Medical School, Avenida Dr Arnaldo, 455, 01246 903, Sao Paulo SP, Brazil
    Eur Respir J 32:61-9. 2008
    ....
  41. ncbi Matrix metalloproteinases and their tissue inhibitors in preterm perinatal complications
    Julia V Cockle
    Perinatal Research Group, Leeds, United Kingdom
    Reprod Sci 14:629-45. 2007
    ..MMPs are involved in the perinatal complications of prematurity and are potential targets for therapeutic intervention. Functional MMP genetic polymorphisms may assist in identifying patients at risk of complications...
  42. ncbi Evidence of in vitro differential secretion of 72 and 92 kDa type IV collagenases after selective exposure to lipopolysaccharide in human fetal membranes
    Guadalupe Garcia-Lopez
    Direction of Research, Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes, Mexico City 11000, Mexico
    Mol Hum Reprod 13:409-18. 2007
    ....
  43. ncbi The plasminogen activator and matrix metalloproteinase systems in colorectal cancer: relationship to tumour pathology
    E A Baker
    Professorial Unit of Surgery, University Hospital of North Tees, Stockton on Tees, TS19 8P, UK
    Eur J Cancer 39:981-8. 2003
    ....
  44. ncbi The activity of matrix metalloproteinases (MMPS) and tissue inhibitors of metalloproteinases (TIMPs) in mammary tumors of dogs and rats
    Kouji Kawai
    Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113 8657, Japan
    J Vet Med Sci 68:105-11. 2006
    ....
  45. ncbi Matrix metalloproteinases (MMPs) in health and disease: an overview
    Charles J Malemud
    Division of Rheumatic Diseases, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
    Front Biosci 11:1696-701. 2006
    ..MMP activity is regulated by a group of endogenous proteins, called, tissue inhibitor of metalloproteinases (TIMPs) that bind to active and alternative sites of the activated MMP...
  46. ncbi Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function
    Merry L Lindsey
    Division of Cardiothoracic Surgery Research, Room 629, Strom Thurmond Research Building, 770 MUSC Complex, Medical University of South Carolina, Charleston, SC 29425, USA
    Cardiovasc Res 66:410-9. 2005
    ..To evaluate the effects of aging on left ventricular (LV) geometry, collagen levels, matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) abundance, and myocardial fibroblast function...
  47. ncbi Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers
    Stephanie Curran
    Department of Pathology, University of Aberdeen, Aberdeen, United Kingdom
    Clin Cancer Res 10:8229-34. 2004
    ..Therefore, to understand their role in tumor invasion, it is necessary to evaluate them collectively...
  48. ncbi Association of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-4 in cerebrospinal fluid with blood-brain barrier dysfunction in patients with eosinophilic meningitis caused by Angiostrongylus cantonensis
    Hung Chin Tsai
    Section of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital 386, Kaohsiung City, Taiwan, Republic of China
    Am J Trop Med Hyg 78:20-7. 2008
    ..Activity of MMP-9 in CSF of patients could not be completely inhibited because of the decrease of TIMP-4, which may cause BBB dysfunction, as shown by higher Q(Alb) values in patients...
  49. ncbi Matrix metalloproteinases in peripheral vascular disease
    Mark J Hobeika
    Department of Surgery, New York University School of Medicine, New York, NY, USA
    J Vasc Surg 45:849-57. 2007
    ..In addition, the importance of MMPs in the future diagnosis and treatment of peripheral vascular disease is discussed...
  50. ncbi Structural properties of matrix metalloproteinases
    W Bode
    Max Planck Institut fur Biochemie, Martinsried, Germany
    Cell Mol Life Sci 55:639-52. 1999
    ..A multitude of reviews surveying work done on all aspects of MMPs have appeared in recent years, but none of them has focused on the three-dimensional structures. This review was written to close the gap...
  51. ncbi Anabolic and catabolic gene expression pattern analysis in normal versus osteoarthritic cartilage using complementary DNA-array technology
    T Aigner
    Cartilage Research, Department of Pathology, University of Erlangen Nuremberg, Erlangen, Germany
    Arthritis Rheum 44:2777-89. 2001
    ..To understand changes in gene expression levels that occur during osteoarthritic (OA) cartilage degeneration, using complementary DNA (cDNA)-array technology...
  52. pmc The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis
    C Chang
    Department of Anatomy, Box 0452, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0452, USA
    Trends Cell Biol 11:S37-43. 2001
    ..We also discuss the evolving concept of how MMPs might regulate stem cell fate during tumor development...
  53. ncbi Electroporative alpha-MSH gene transfer attenuates thioacetamide-induced murine hepatic fibrosis by MMP and TIMP modulation
    C H Wang
    Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan
    Gene Ther 13:1000-9. 2006
    ..Its collagenolytic effect might be attributed to MMP and TIMP modulation. Hence, alpha-MSH gene therapy may be an effective therapeutic modality against liver fibrosis with potential clinical use...
  54. ncbi Quantitative analysis of mRNA expression of TIMPs in the periprosthetic interface tissue of loose hips by real-time PCR system
    K Sasaki
    Department of Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata, 990 9585, Japan
    J Biomed Mater Res 58:605-12. 2001
    ....
  55. ncbi Expression of matrix metalloproteinases in cyclosporin-treated gingival fibroblasts is regulated by transforming growth factor (TGF)-beta1 autocrine stimulation
    P Cotrim
    Discipline of Oral Pathology, University of Campinas Dental School, Piracicaba, Sao Paulo, Brazil
    J Periodontol 73:1313-22. 2002
    ....
  56. ncbi Steps involved in activation of the pro-matrix metalloproteinase 9 (progelatinase B)-tissue inhibitor of metalloproteinases-1 complex by 4-aminophenylmercuric acetate and proteinases
    Y Ogata
    Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City 66160 7421, USA
    J Biol Chem 270:18506-11. 1995
    The precursor of matrix metalloproteinase 9 (pro-MMP-9, progelatinase B) noncovalently binds to tissue inhibitor of metalloproteinases (TIMP)-1 through the C-terminal domain of each molecule. We have isolated the proMMP-9...
  57. ncbi MMP/TIMP imbalance in amniotic fluid during PROM: an indirect support for endogenous pathway to membrane rupture
    S J Fortunato
    Perinatal Research Center, Women s Health Research and Education Foundation, Nashville, TN, USA
    J Perinat Med 27:362-8. 1999
    ..This study examines the levels of the gelatinases and their natural inhibitors (tissue inhibitor of matrix metalloproteinases-TIMPs) in the amniotic fluid during PROM, preterm labor (PTL) and at term...
  58. pmc H2S ameliorates oxidative and proteolytic stresses and protects the heart against adverse remodeling in chronic heart failure
    Paras K Mishra
    Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky, USA
    Am J Physiol Heart Circ Physiol 298:H451-6. 2010
    ..The levels of ADAM-12, apoptosis, and fibrosis were robust and integrin were decreased in AVF hearts. The treatment with H(2)S donor attenuated the fibrosis, apoptosis, and decrease in integrin...
  59. ncbi Human chorionic gonadotropin stimulates matrix metalloproteinases-2 and -9 in cytotrophoblastic cells and decreases tissue inhibitor of metalloproteinases-1, -2, and -3 in decidualized endometrial stromal cells
    Herbert Fluhr
    Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany
    Fertil Steril 90:1390-5. 2008
    To investigate the influence of hCG on trophoblastic matrix metalloproteinases (MMPs) -2 and -9 as well as endometrial tissue inhibitor of metalloproteinases (TIMPs) -1, -2, and -3.
  60. ncbi Functional analysis of matrix metalloproteinases and tissue inhibitors of metalloproteinases differentially expressed by variants of human HT-1080 fibrosarcoma exhibiting high and low levels of intravasation and metastasis
    Juneth J Partridge
    Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 282:35964-77. 2007
    ..Collectively, these findings demonstrate that tumor-derived MMPs may have protective functions in cancer cell intravasation, i.e. not promoting but rather catalytically interfering with the early stages of cancer dissemination...
  61. ncbi Tissue inhibitor of metalloproteinases in oral squamous cell carcinomas - a therapeutic target?
    Mario Pérez-Sayáns García
    Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Dentistry, Instituto de Investigación Sanitaria de Santiago, Santiago de Compostela, Spain
    Cancer Lett 323:11-9. 2012
    ....
  62. ncbi Matrix metalloproteinases and the ontogeny of scarless repair: the other side of the wound healing balance
    Ziv M Peled
    Children s Surgical Research Program, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA 94305 5148, USA
    Plast Reconstr Surg 110:801-11. 2002
    ..Furthermore, our data suggest that the differential expression of gelatinase B (MMP-9) may be mediated by the fetal fibroblasts themselves...
  63. ncbi Tissue inhibitor of metalloproteinases (TIMPs) in heart failure
    Linn Moore
    Department of Physiology, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Heritage Medical Research Centre, Edmonton, AB, Canada
    Heart Fail Rev 17:693-706. 2012
    ..by a balance in the function of matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs)...
  64. pmc Imbalances between matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in maternal serum during preterm labor
    Inge Tency
    Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
    PLoS ONE 7:e49042. 2012
    ..Therefore, the purpose of this study was to determine serum concentrations of MMP-3, MMP-9 and all four TIMPs as well as MMP:TIMP ratios during term and preterm labor...
  65. ncbi Evaluation of the expression of metalloproteinases 2 and 9 and their tissue inhibitors in colon cancer cells treated with phytic acid
    Małgorzata Kapral
    Department of Biochemistry, Medical University of Silesia, Narcyzow 1, 41 200 Sosnowiec, Poland
    Acta Pol Pharm 67:625-9. 2010
    ..The results of this study show that IP6 modulates MMP-2, TIMP-1 and TIMP-2 genes expression in colon cancer cells at the transcriptional level in a way dependent on its concentration and time of interaction...
  66. pmc Ancylostoma ceylanicum excretory-secretory protein 2 adopts a netrin-like fold and defines a novel family of nematode proteins
    Kaury Kucera
    Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA
    J Mol Biol 408:9-17. 2011
    ..Together, our results suggest that AceES-2 defines a novel family of nematode netrin-like proteins, which may function to modulate the host immune response to hookworm and other parasites...
  67. pmc Mice with tissue inhibitor of metalloproteinases 4 (Timp4) deletion succumb to induced myocardial infarction but not to cardiac pressure overload
    Ilpo Koskivirta
    Department of Medical Biochemistry and Genetics, University of Turku, FI 20520 Turku, Finland
    J Biol Chem 285:24487-93. 2010
    b>Tissue inhibitor of metalloproteinases 4 (TIMP4) is expressed highly in heart and found dysregulated in human cardiovascular diseases...
  68. ncbi Interplay of matrix metalloproteinases, tissue inhibitors of metalloproteinases and their regulators in cardiac matrix remodeling
    Y Y Li
    1750 Biomedical Science Tower, Cardiovascular Institute, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Cardiovasc Res 46:214-24. 2000
    ..It is therefore suggested that the interplay of MMPs and their regulators is important in the development of the heart failure phenotype, and myocardial fibrosis in heart failure may be modified by modulating MMP activity...
  69. doi Transcriptional regulation of TIMPs in ascending aorta aneurysms
    Kostas Tsarouhas
    Department of Virology, Medical School, University of Crete, Heraklion, Crete, Greece
    Thromb Res 126:399-405. 2010
    ..Surprisingly, the tissue inhibitor of metalloproteinases (TIMP)-3 was significantly more expressed in dilated aortic tissue compared to control tissue, ..
  70. pmc Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer
    F J G M Kubben
    Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
    Br J Cancer 95:744-51. 2006
    ..We conclude that MMP-related SNPs, especially MMP-7(-181A>G) and TIMP-2(303C>T), may be helpful in identifying gastric cancer patients with a poor clinical outcome...
  71. ncbi Activation of the 92-kDa gelatinase by stromelysin and 4-aminophenylmercuric acetate. Differential processing and stabilization of the carboxyl-terminal domain by tissue inhibitor of metalloproteinases (TIMP)
    S D Shapiro
    Department of Medicine, Washington University School of Medicine, Jewish Hospital, St Louis, Missouri 63110
    J Biol Chem 270:6351-6. 1995
    ..Macrophages synthesize and secrete this proteinase as a proenzyme in association with tissue inhibitor of metalloproteinases (TIMP) (92TIMP), whereas neutrophils store and release it from secondary granules as a TIMP-free ..
  72. ncbi Secretion of matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases into follicular fluid during follicle development in equine ovaries
    S C Riley
    Obstetrics and Gynaecology Section, Department of Reproductive and Developmental Sciences, University of Edinburgh, 37 Chalmers Street, Edinburgh EH3 9ET, UK
    Reproduction 121:553-60. 2001
    ..The MMPs and TIMPs are likely to be involved in the regulation of the breakdown of extracellular matrix during tissue remodelling for follicle development and migration to the ovulation fossa in mares...
  73. ncbi Matrix metalloproteinases and mesangial remodeling in light chain-related glomerular damage
    John Keeling
    Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA
    Kidney Int 68:1590-603. 2005
    ..Alterations of the mesangial ECM in AL-amyloidosis (AL-Am) and light chain deposition disease (LCDD) are crucial in their pathogeneses as two divergent entities...
  74. ncbi Involvement of AP1 and PEA3 binding sites in the regulation of murine tissue inhibitor of metalloproteinases-1 (TIMP-1) transcription
    D R Edwards
    Department of Pharmacology and Therapeutics, University of Calgary, Canada
    Biochim Biophys Acta 1171:41-55. 1992
    Transcription of tissue inhibitor of metalloproteinases-1 (TIMP-1), a secreted protein that regulates the activities of the metalloproteinases, collagenase and stromelysin, is activated by serum growth factors...
  75. ncbi Temporal regulation of extracellular matrix components in transition from compensatory hypertrophy to decompensatory heart failure
    V S Mujumdar
    Department of Physiology and Biophysics, and Center of Excellence in Cardiovascular Renal Research, University of Mississippi Medical Center, Jackson 39216 4505, USA
    J Hypertens 17:261-70. 1999
    ..Collagen is induced during the transition from compensatory hypertrophy to heart failure. We hypothesized that cardiac stiffness during decompensatory hypertrophy is partly due to a decreased elastin:collagen ratio...
  76. ncbi In vitro synthesis of the active tissue inhibitor of metalloproteinases encoded by a complementary DNA from virus-infected murine fibroblasts
    B Coulombe
    Institut du Cancer de Montreal, Quebec, Canada
    J Biol Chem 263:1439-43. 1988
    ..described the characterization and expression of a murine gene highly homologous to the human tissue inhibitor of metalloproteinases/erythroid potentiating activity (TIMP/EPA) gene...
  77. ncbi Localization of matrix metalloproteinases, (MMPs) their tissue inhibitors, and vascular endothelial growth factor (VEGF) in growth plates of children and adolescents indicates a role for MMPs in human postnatal growth and skeletal maturation
    G Haeusler
    Pediatric Department, Medical University of Vienna, Austria
    Calcif Tissue Int 76:326-35. 2005
    ....
  78. ncbi Transcription factor early growth response 1 activity up-regulates expression of tissue inhibitor of metalloproteinases 1 in human synovial fibroblasts
    Wilhelm K Aicher
    University Hospital Tubingen, Tubingen, Germany
    Arthritis Rheum 48:348-59. 2003
    To investigate the regulatory potential of early growth response 1 (Egr-1) on tissue inhibitor of metalloproteinases 1 (TIMP-1) expression in synovial fibroblasts.
  79. ncbi Tissue inhibitor of metalloproteinases-4 (TIMP-4) gene expression is increased in human osteoarthritic femoral head cartilage
    Wensheng Huang
    Departments of Medicine, Research Center and Notre Dame Hospital of the Centre hospitalier de l université de Montréal CHUM, Montreal, Quebec, Canada H2L 4M1
    J Cell Biochem 85:295-303. 2002
    b>Tissue inhibitor of metalloproteinases-4 (TIMP-4), the newest member of the TIMP family, blocks the activities of several matrix metalloproteinases (MMPs) implicated in the arthritic cartilage erosion...
  80. ncbi Cell density-dependent regulation of matrix metalloproteinase and TIMP expression in differently tumorigenic breast cancer cell lines
    Beatrice E Bachmeier
    Department Clinical Chemistry and Clinical Biochemistry, Hospital of Surgery, Ludwig Maximilians University, Nussbaumstr 20, D 80336 MUnchen, Germany
    Exp Cell Res 305:83-98. 2005
    ..Our data provide clear evidence that cell density regulates major MMPs and TIMPs which are controlled by AP-1 activity so that ultimately a major regulation pathway for the control of the invasive potential of tumor cells is presented...
  81. pmc Human 72-kilodalton type IV collagenase forms a complex with a tissue inhibitor of metalloproteases designated TIMP-2
    G I Goldberg
    Division of Dermatology, Washington University School of Medicine, Saint Louis, MO 63110
    Proc Natl Acad Sci U S A 86:8207-11. 1989
    ..Both activity and activation of the complex can be completely inhibited by further addition of stoichiometric quantities of purified TIMP-2 or recombinant TIMP...
  82. ncbi Cellular turnover in the mammary gland is correlated with systemic levels of progesterone and not 17beta-estradiol during the estrous cycle
    J E Fata
    Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9
    Biol Reprod 65:680-8. 2001
    ..We propose that the cyclical turnover of epithelial cells within the adult mammary tissue is a sum of spatial and functional coordination of hormonal and matrix regulatory factors...
  83. doi Expression of genes encoding matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in normal and diseased canine mitral valves
    H Aupperle
    Institut für Veterinär Pathologie, Veterinärmedizinische Fakultät, Universitat Leipzig, An den Tierkliniken 33, 04103 Leipzig
    J Comp Pathol 140:271-7. 2009
    ..MMPs and TIMPs are therefore likely to be involved in extracellular matrix metabolism in normal canine MVs and there are significant alterations in the expression of genes encoding these molecules during CVD...
  84. pmc Expression of metalloproteinases and their inhibitors in primary pulmonary carcinomas
    S J Urbanski
    Department of Pathology, University of Calgary, Alberta, Canada
    Br J Cancer 66:1188-94. 1992
    ..The possible prognostic significance of the expression of the latter two enzymes by carcinomas remains to be established...
  85. ncbi Global gene expression profiles reveal an increase in mRNA levels of collagens, MMPs, and TIMPs in late radiation enteritis
    Carine Strup-Perrot
    Laboratoire UPRES EA 27 10 Radiosensibilité des Tumeurs et Tissus Sains, Institut Gustave Roussy Institut de Radioprotection et de Sureté Nucléaire, 94805 Villejuif, France
    Am J Physiol Gastrointest Liver Physiol 287:G875-85. 2004
    ..This demonstrates that established fibrotic tissue is not scarred fixed tissue but is subjected to a dynamic remodeling process...
  86. ncbi Physical linkage of the A-raf-1, properdin, synapsin I, and TIMP genes on the human and mouse X chromosomes
    J M Derry
    MRC Molecular Neurobiology Unit, MRC Centre, Cambridge, United Kingdom
    Genomics 12:632-8. 1992
    Genes encoding the neuron-specific phosphoprotein synapsin I (SYN1), the glycoprotein tissue inhibitor of metalloproteinases (TIMP), the proto-oncogene A-raf-1 (ARAF1), and properdin (PFC), a positive regulator of the alternative pathway ..
  87. ncbi Expression profiling of metalloproteinases and their inhibitors in cartilage
    Lara Kevorkian
    University of East Anglia, Norwich, UK
    Arthritis Rheum 50:131-41. 2004
    To profile the expression of all known members of the matrix metalloproteinase (MMP), ADAMTS, and tissue inhibitor of metalloproteinases (TIMP) gene families in normal cartilage and cartilage from patients with osteoarthritis (OA).
  88. ncbi Analysis of expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human ciliary body after latanoprost
    Dong Jin Oh
    Laboratory for Molecular Ophthalmology, Wills Eye Hospital, Philadelphia, Pennsylvania, USA
    Invest Ophthalmol Vis Sci 47:953-63. 2006
    ..To determine the effect of latanoprost on the expression of human matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the ciliary body...
  89. ncbi The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis
    Takeshi Itoh
    Discovery Research Laboratories, Shionogi and Co, Ltd, Toyonaka City, Osaka, Japan
    J Immunol 169:2643-7. 2002
    ..These results indicated a suppressive role of MMP-2 and a pivotal role of MMP-9 in the development of inflammatory joint disease...
  90. ncbi Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4
    J Greene
    Human Genome Sciences, Inc, Rockville, Maryland 20850 3338, USA aecom yu edu
    J Biol Chem 271:30375-80. 1996
    ..This unique expression pattern suggests that TIMP-4 may function in a tissue-specific fashion in extracellular matrix homeostasis...
  91. ncbi Tissue inhibitors of metalloproteinase expression in human breast cancer: TIMP-3 is associated with adjuvant endocrine therapy success
    Paul N Span
    Department of Chemical Endocrinology, University Medical Center Nijmegen, Nijmegen, The Netherlands
    J Pathol 202:395-402. 2004
    ..0003). Thus, high tumour levels of the matrix metalloproteinases inhibitor and pro-apoptotic factor TIMP-3 are associated with successful tamoxifen treatment of patients with breast cancer...
  92. ncbi Molecular cloning of an ovine ovarian tissue inhibitor of metalloproteinases: ontogeny of messenger ribonucleic acid expression and in situ localization within preovulatory follicles and luteal tissue
    G W Smith
    Department of Animal Science, University of Missouri, Columbia 65211
    Endocrinology 134:344-52. 1994
    Secretion of a tissue inhibitor of metalloproteinases (TIMP-1) is initiated by ovine preovulatory follicles after the gonadotropin surge. In addition, TIMP-1 is a major secretory product of ovine corpora lutea...
  93. pmc Matrix metalloproteinases and their tissue inhibitors direct cell fate during cancer development
    C V Hojilla
    Ontario Cancer Institute, University Health Network, Toronto, Canada
    Br J Cancer 89:1817-21. 2003
    ..The extracellular nature of the metalloproteinase axis situates it as a master regulator of cell fate...
  94. ncbi Endometrial TIMP-4 mRNA is high at midcycle and in hyperplasia, but down-regulated in malignant tumours. Coordinated expression with MMP-26
    R Pilka
    Department of Obstetrics and Gynaecology, University Hospital, S 221 85 Lund, Sweden
    Mol Hum Reprod 10:641-50. 2004
    ..Similarities in the cyclic patterns of TIMP-4 mRNA and MMP-26 mRNA, together with the fact that TIMP-4 is a potent inhibitor of MMP-26, suggest a functional relationship, and furthermore a role in human implantation...
  95. ncbi Structural basis of the matrix metalloproteinases and their physiological inhibitors, the tissue inhibitors of metalloproteinases
    Wolfram Bode
    Max Planck Institut fur Biochemie, Am Klopferspitz 18a, D 82152 Martinsried, Germany
    Biol Chem 384:863-72. 2003
    ..This review will outline our current structural knowledge of the MMPs and the TIMPs...
  96. ncbi Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinases TIMP-3 and -4 in benign endometrium and endometrial cancer
    Renuka Tunuguntla
    Department of Obstetrics Gynecology, University of Florida, Gainesville, FL 32610, USA
    Gynecol Oncol 89:453-9. 2003
    ....
  97. pmc Cirrhosis: new research provides a basis for rational and targeted treatments
    John P Iredale
    Division of Infection, Inflammation and Repair, University of Southampton, Southampton General Hospital, Southampton SO16 6YD
    BMJ 327:143-7. 2003
  98. ncbi In situ gene expression and localization of metalloproteinases MMP1, MMP2, MMP3, MMP9, and their inhibitors TIMP1 and TIMP2 in human renal cell carcinoma
    Venugopal Bhuvarahamurthy
    Department of Urology, University Hospital Charite, CCM, Humboldt University, Berlin, Germany
    Oncol Rep 15:1379-84. 2006
    ..Due to the small sample size further investigations need to be done to prove a statistical significant correlation between the MMP/TIMP expression and clinicopathological parameters...
  99. ncbi Novel functions of TIMPs in cell signaling
    Rosemarie Chirco
    Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, Michigan 48201, USA
    Cancer Metastasis Rev 25:99-113. 2006
    ....
  100. pmc Identification, regulation and role of tissue inhibitor of metalloproteinases-4 (TIMP-4) in human platelets
    Anna Radomski
    Department of Pharmacology, University of Alberta, 9 50 Medical Sciences Building, Edmonton, Ontario, Canada T6G 2H7
    Br J Pharmacol 137:1330-8. 2002
    ..11. Human rTIMP-4 exerted a biphasic effect on HT-1080 cells-induced aggregation. 12. Thus, TIMP-4 is the major intraplatelet MMP inhibitor and it is involved in regulation of platelet aggregation and recruitment...
  101. ncbi mRNA expression of matrix metalloproteases and their inhibitors differs in subtypes of renal cell carcinomas
    T Hagemann
    Department of Haematology Oncology, Georg August University Robert Koch Str 40, D 37075, Gottingen, Germany
    Eur J Cancer 37:1839-46. 2001
    ....

Research Grants75

  1. METALLOPROTEASES IN CONNECTIVE TISSUE MATRIX BREAKDOWN
    Hideaki Nagase; Fiscal Year: 1993
    ..this will be approached by identification of the side chains involved in binding to tissue inhibitor of metalloproteinases 1 (TIMP-1) and in reaction with alpha2- macroglobulin by a competitive binding "label selection" ..
  2. RHESUS PROPAGATION BY INTRACYTOPLASMIC NUCLEAR INJECTION (SUPPLEMENT)
    Gerald Schatten; Fiscal Year: 2000
    ..In International Symposium on Ovulation Evolving and Clinical Concepts (held in Salt Lake City, UT, September 24-27, 1998), p 33 (abstract #1). ..
  3. ACTIVATION OF COLLAGENASE IN RHEUMATOID ARTHRITIS
    L Windsor; Fiscal Year: 1999
    ..activation of collagenase-1 will be identified and characterized by alpha2-macroglobulin and TIMP (tissue inhibitor of metalloproteinases) capture techniques as well as by their reactivity in a fluorescent maleimide...
  4. Matrix Metalloproteinases and the Blood-Brain Barrier
    Gary Rosenberg; Fiscal Year: 2009
    ..Matrix metalloproteinase inhibitors will be studied that have the potential to be used to prevent the death of vulnerable cells in the white matter. ..
  5. ACTIVATION OF COLLAGENASE IN RHEUMATOID ARTHRITIS
    L Windsor; Fiscal Year: 2001
    ..activation of collagenase-1 will be identified and characterized by alpha2-macroglobulin and TIMP (tissue inhibitor of metalloproteinases) capture techniques as well as by their reactivity in a fluorescent maleimide...
  6. Matrix Metalloproteinases and the Blood-Brain Barrier
    GARY ALLEN ROSENBERG; Fiscal Year: 2010
    ..Matrix metalloproteinase inhibitors will be studied that have the potential to be used to prevent the death of vulnerable cells in the white matter. ..
  7. ACTIVATION OF COLLAGENASE IN RHEUMATOID ARTHRITIS
    L Windsor; Fiscal Year: 2000
    ..activation of collagenase-1 will be identified and characterized by alpha2-macroglobulin and TIMP (tissue inhibitor of metalloproteinases) capture techniques as well as by their reactivity in a fluorescent maleimide...
  8. 92K-GL (MMP 9) AND THE INVASIVE PHENOTYPE
    MARTIN BODDEN; Fiscal Year: 1999
    ..The combination of the studies proposed in this application will provide a better understanding of the role of 92K-GL and TIMP-l, as well as other MMPs, in the invasive phenotype of human cancers of oral and other origins. ..
  9. PA/PLASMIN/GELATINASE CASCADE IN DIABETIC NEPHROPATHY
    WILLIAM BARICOS; Fiscal Year: 2000
    ....
  10. PLASMIN & GELATINASE & ECM CATABOLISM BY MESANGIAL CELLS
    WILLIAM BARICOS; Fiscal Year: 1992
    ....
  11. PA/PLASMIN/GELATINASE CASCADE IN DIABETIC NEPHROPATHY
    WILLIAM BARICOS; Fiscal Year: 1999
    ....
  12. Sertoli cell injury and mechanisms of testicular germ cell apoptosis
    John H Richburg; Fiscal Year: 2012
    ..It is anticipated that the mechanistic insights provided from this work will be useful for predicting and preventing human reproductive health risks to chemicals, such as the phthalates, found ubiquitously in the environment. ..
  13. Sertoli cell injury and mechanisms of testicular germ cell apoptosis
    John H Richburg; Fiscal Year: 2010
    ..It is anticipated that the mechanistic insights provided from this work will be useful for predicting and preventing human reproductive health risks to chemicals, such as the phthalates, found ubiquitously in the environment. ..
  14. Sertoli cell injury and mechanisms of testicular germ cell apoptosis
    JOHN RICHBURG; Fiscal Year: 2009
    ..It is anticipated that the mechanistic insights provided from this work will be useful for predicting and preventing human reproductive health risks to chemicals, such as the phthalates, found ubiquitously in the environment. ..
  15. Sertoli cell injury and mechanisms of testicular germ cell apoptosis
    John H Richburg; Fiscal Year: 2011
    ..It is anticipated that the mechanistic insights provided from this work will be useful for predicting and preventing human reproductive health risks to chemicals, such as the phthalates, found ubiquitously in the environment. ..
  16. ALPHA-2 MACROGLOBULIN RECEPTOR, RAP, AND PREECLAMPSIA
    Dudley Strickland; Fiscal Year: 1993
    ..determine if the alpha2MR mediates catabolism of metalloproteinase complexed to their inhibitor, tissue inhibitor of metalloproteinases (TIMP). The second specific alm is designed to explore the role of RAP in trophoblast invasion...
  17. KERATOCYTE COLLAGENASE INDUCED VIA FIBRONECTIN RECEPTOR
    Sandra Masur; Fiscal Year: 1992
    ....
  18. Matrix Metalloproteinases and the Blood-Brain Barrier
    Gary Rosenberg; Fiscal Year: 2004
    ..Understanding the molecular events in the BBB disruption by MMPs will provide a rational basis for drug design, and will lead to novel treatments in many important neurological diseases. ..
  19. Matrix Metalloproteinases and the Blood-Brain Barrier
    Gary Rosenberg; Fiscal Year: 2005
    ..Understanding the molecular events in the BBB disruption by MMPs will provide a rational basis for drug design, and will lead to novel treatments in many important neurological diseases. ..
  20. Matrix Metalloproteinases and the Blood-Brain Barrier
    Gary Rosenberg; Fiscal Year: 2003
    ..Understanding the molecular events in the BBB disruption by MMPs will provide a rational basis for drug design, and will lead to novel treatments in many important neurological diseases. ..
  21. Matrix Metalloproteinases and the Blood-Brain Barrier
    Gary Rosenberg; Fiscal Year: 2006
    ..Understanding the molecular events in the BBB disruption by MMPs will provide a rational basis for drug design, and will lead to novel treatments in many important neurological diseases. ..
  22. Human Cytomegalovirus-Induced Inhibition of Cytotrophoblast Invasion
    Cindy Morris; Fiscal Year: 2009
    ..Defining how HCMV impairs EVT invasion is of major importance to the reproductive community and may provide additional therapeutic targets to maintain viable pregnancy. ..
  23. Human Cytomegalovirus-Induced Inhibition of Cytotrophoblast Invasion
    Cindy Morris; Fiscal Year: 2009
    ..Defining how HCMV impairs EVT invasion is of major importance to the reproductive community and may provide additional therapeutic targets to maintain viable pregnancy. ..
  24. TNF-alpha Signaling in Silica-Induced Lung Fibrosis
    Luis Ortiz; Fiscal Year: 2005
    ..3). To determine whether overexpression of Tissue Inhibitor of Metalloproteinase 1 (TIMP-1) in mouse lung exacerbates silica- induced lung injury. ..
  25. TNF-alpha Signaling in Silica-Induced Lung Fibrosis
    Luis Ortiz; Fiscal Year: 2002
    ..3). To determine whether overexpression of Tissue Inhibitor of Metalloproteinase 1 (TIMP-1) in mouse lung exacerbates silica- induced lung injury. ..
  26. TNF-alpha Signaling in Silica-Induced Lung Fibrosis
    Luis Ortiz; Fiscal Year: 2003
    ..3). To determine whether overexpression of Tissue Inhibitor of Metalloproteinase 1 (TIMP-1) in mouse lung exacerbates silica- induced lung injury. ..
  27. TNF-alpha Signaling in Silica-Induced Lung Fibrosis
    Luis Ortiz; Fiscal Year: 2002
    ..3). To determine whether overexpression of Tissue Inhibitor of Metalloproteinase 1 (TIMP-1) in mouse lung exacerbates silica- induced lung injury. ..
  28. TNF-alpha Signaling in Silica-Induced Lung Fibrosis
    Luis Ortiz; Fiscal Year: 2004
    ..3). To determine whether overexpression of Tissue Inhibitor of Metalloproteinase 1 (TIMP-1) in mouse lung exacerbates silica- induced lung injury. ..
  29. TNF-alpha Signaling in Silica-Induced Lung Fibrosis
    Luis Ortiz; Fiscal Year: 2006
    ..3). To determine whether overexpression of Tissue Inhibitor of Metalloproteinase 1 (TIMP-1) in mouse lung exacerbates silica- induced lung injury. ..
  30. DNA CAPILLARY ELECTROPHORESIS PROTOCOLS AND PROCESSES
    Michael Morris; Fiscal Year: 2001
    ..Second, homocysteine in pathologically relevant concentrations induced the expression of tissue inhibitor of metalloproteinases-1 (TIMP- 1) and alpha1 (I) procollagen in a hepatic stellate cell line and collagen production in ..
  31. DNA CAPILLARY ELECTROPHORESIS PROTOCOLS AND PROCESSES
    Michael Morris; Fiscal Year: 2002
    ..Second, homocysteine in pathologically relevant concentrations induced the expression of tissue inhibitor of metalloproteinases-1 (TIMP- 1) and alpha1 (I) procollagen in a hepatic stellate cell line and collagen production in ..
  32. COLLAGENOLYSIS-DRIVEN MOLECULAR MOTORS IN CELL MIGRATION AND MATRIX REMODELING
    Gregory Goldberg; Fiscal Year: 2009
    ..The goal of this proposal is to provide for a better understanding of the molecular mechanisms of spatially regulated peri-cellular proteolysis catalyzed by MMPs and its functional role in numerous normal and pathological conditions. ..
  33. COLLAGENOLYSIS-DRIVEN MOLECULAR MOTORS IN CELL MIGRATION AND MATRIX REMODELING
    Gregory I Goldberg; Fiscal Year: 2010
    ..The goal of this proposal is to provide for a better understanding of the molecular mechanisms of spatially regulated peri-cellular proteolysis catalyzed by MMPs and its functional role in numerous normal and pathological conditions. ..
  34. REGULATION OF METALLOPROTEINASE ACTIVITY BY TIMP-2
    MICHAEL BANDA; Fiscal Year: 1992
    ..Initially, the tissue inhibitor of metalloproteinases (TIMP or TIMP-1) was the only inhibitor of its kind that was suspected to be involved in the ..
  35. ALTERED METHIONINE METABOLISM IN ALCOHOLIC LIVER INJURY
    Shelly Lu; Fiscal Year: 2004
    ..Second, homocysteine in pathologically relevant concentrations induced the expression of tissue inhibitor of metalloproteinases-4 (TIMP- 1) and a 1(I) procollagen in a hepatic stellate cell line and collagen production in ..
  36. Mechanisms of Reduced Fecundity in Endometriosis: A role for MMPs and TIMPs
    KATHY L TIMMS; Fiscal Year: 2010
    ..As it is known that TIMP-1 highly regulates MMPs critical for follicular development, ovulation and embryo development, we propose endometriotic TIMP-1 is blocking MMPs required for normal function and reducing fecundity. ..
  37. Mechanisms of Reduced Fecundity in Endometriosis: A role for MMPs and TIMPs
    KATHY TIMMS; Fiscal Year: 2009
    ..As it is known that TIMP-1 highly regulates MMPs critical for follicular development, ovulation and embryo development, we propose endometriotic TIMP-1 is blocking MMPs required for normal function and reducing fecundity. ..
  38. ALTERED METHIONINE METABOLISM IN ALCOHOLIC LIVER INJURY
    Shelly Lu; Fiscal Year: 2005
    ..Second, homocysteine in pathologically relevant concentrations induced the expression of tissue inhibitor of metalloproteinases-4 (TIMP- 1) and a 1(I) procollagen in a hepatic stellate cell line and collagen production in ..
  39. ALTERED METHIONINE METABOLISM IN ALCOHOLIC LIVER INJURY
    Shelly Lu; Fiscal Year: 2001
    ..Second, homocysteine in pathologically relevant concentrations induced the expression of tissue inhibitor of metalloproteinases-4 (TIMP- 1) and a 1(I) procollagen in a hepatic stellate cell line and collagen production in ..
  40. THE BIOLOGICAL ROLE OF HUMAN TIMP IN MATRIX TURNOVER
    Howard Welgus; Fiscal Year: 1990
    ..b>Tissue inhibitor of metalloproteinases, or TIMP, functions as the major, and probably, only, inhibitor of this entire family of neutral ..
  41. ALTERED METHIONINE METABOLISM IN ALCOHOLIC LIVER INJURY
    Shelly Lu; Fiscal Year: 2002
    ..Second, homocysteine in pathologically relevant concentrations induced the expression of tissue inhibitor of metalloproteinases-4 (TIMP- 1) and a 1(I) procollagen in a hepatic stellate cell line and collagen production in ..
  42. ALTERED METHIONINE METABOLISM IN ALCOHOLIC LIVER INJURY
    Shelly Lu; Fiscal Year: 2003
    ..Second, homocysteine in pathologically relevant concentrations induced the expression of tissue inhibitor of metalloproteinases-4 (TIMP- 1) and a 1(I) procollagen in a hepatic stellate cell line and collagen production in ..
  43. NOVEL ROLE AND REGULATION OF UTERINE TIMPS
    Warren Nothnick; Fiscal Year: 2000
    ..abstract_text> ..
  44. NOVEL ROLE AND REGULATION OF UTERINE TIMPS
    Warren Nothnick; Fiscal Year: 1999
    ..abstract_text> ..
  45. Endothelial Myocyte Matrix in Cardiac Remodeling
    Suresh C Tyagi; Fiscal Year: 2010
    ....
  46. Inducible Macrophage Specific Gene Expression in Diseases
    JEANINE D ARMIENTO; Fiscal Year: 2009
    ..We will also examine the consequences of the absence of macrophage tissue inhibitor of metalloproteinases-3 in lung injury.
  47. Endothelial Myocyte Matrix in Cardiac Remodeling
    SURESH TYAGI; Fiscal Year: 2009
    ....
  48. Endothelial Myocyte Matrix in Cardiac Remodeling
    SURESH TYAGI; Fiscal Year: 2009
    ....
  49. Inducible Macrophage Specific Gene Expression in Diseases
    JEANINE M D apos ARMIENTO; Fiscal Year: 2010
    ..We will also examine the consequences of the absence of macrophage tissue inhibitor of metalloproteinases-3 in lung injury.
  50. Matrix Metalloproteinases and Spinal Cord Injury
    Linda Noble; Fiscal Year: 2009
    ....
  51. Matrix Metalloproteinases and Spinal Cord Injury
    Linda J Noble; Fiscal Year: 2010
    ....
  52. MECHANISMS IN THE REMODELING OF LUNG STRUCTURE
    Robert Senior; Fiscal Year: 1990
    ..elastin, human neutrophil elastase, type IV collagen, human interstitial collagenase, human tissue inhibitor of metalloproteinases (TIMP) and a newly discovered elastogenic factor released by pulmonary artery smooth muscle cells...
  53. HUMAN ALVEOLAR MACROPHAGE ELASTASES IN EMPHYSEMA
    Harold Chapman; Fiscal Year: 1993
    ..The results should provide a clearer view of the role of macrophages in emphysema and a sound foundation for future efforts both to monitor and to modulate macrophage proteolysis in vivo...
  54. EXTRACELLULAR MATRIX DEGRADATION IN SKIN
    George Stricklin; Fiscal Year: 1990
    ..These degradative enzymes are in turn regulated by a proteinase inhibitor, Tissue Inhibitor of MetalloProteinases or TIMP...
  55. METALLOPROTEINASES AND OVARIAN FUNCTION
    Thomas Curry; Fiscal Year: 1999
    ....
  56. Matrix Metalloproteinases in Hepatic Ischemia and Reperfusion Injury
    Ana J Coito; Fiscal Year: 2010
    ..relative contribution in normal and steatotic liver IRI;and (3) To dissect the mechanisms by which tissue inhibitor of metalloproteinases-1 affects IRI in normal and in steatotic livers...
  57. The Role of Leptin in Liver Fibrogenesis
    Frank A Anania; Fiscal Year: 2010
    ..The project seeks to determine whether adiponectin can act as a protector from the harmful effects of leptin in liver fibrosis. ..
  58. The Role of Leptin in Liver Fibrogenesis
    Frank Anania; Fiscal Year: 2009
    ..The project seeks to determine whether adiponectin can act as a protector from the harmful effects of leptin in liver fibrosis. ..
  59. The Role of Leptin in Liver Fibrogenesis
    Frank Anania; Fiscal Year: 2009
    ..The project seeks to determine whether adiponectin can act as a protector from the harmful effects of leptin in liver fibrosis. ..
  60. CARTILAGE MARKERS IN JOINT FLUID/SERUM AFTER MENISCUS INJURY/TREATMENT
    Bruce Beynnon; Fiscal Year: 1999
    ..To compare the concentration of articular cartilage markers (aggrecan, stromelysin, tissue inhibitor of metalloproteinases (TIMP), procollagen II C-peptide, cartilage and oligiometric matrix protein (COMP) in joint fluid ..
  61. Mechanism of mutant TIMP-3 induced neovascularization
    Michael Tolentino; Fiscal Year: 2004
    ..Specific aim 3: To develop and test gene vectors expressing inhibitors of angiogenesis (angiostatin, endostatin, PEDF) and test their ability to inhibit subretinal neovascularization in the mutant transgenic mouse. ..
  62. Mechanism of mutant TIMP-3 induced neovascularization
    Michael Tolentino; Fiscal Year: 2001
    ..Specific aim 3: To develop and test gene vectors expressing inhibitors of angiogenesis (angiostatin, endostatin, PEDF) and test their ability to inhibit subretinal neovascularization in the mutant transgenic mouse. ..
  63. Neuronal survival, HIV-1 and Astrocyte TIMP-1
    Anuja Ghorpade; Fiscal Year: 2010
    ..Our studies will provide a better understanding of the specific mechanistic contributions of activated astrocytes to HIV-1-neuropathogensis and neuroinflammation. ..
  64. Neuronal survival, HIV-1 and Astrocyte TIMP-1
    Anuja Ghorpade; Fiscal Year: 2009
    ..Our studies will provide a better understanding of the specific mechanistic contributions of activated astrocytes to HIV-1-neuropathogensis and neuroinflammation. ..