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 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. ncbi 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
  10. 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

Research Grants

Detail Information

Publications328 found, 100 shown here

  1. 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
    ....
  2. 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...
  3. 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...
  4. 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...
  5. 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
    ....
  6. 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
    ....
  7. 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...
  8. 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...
  9. ncbi 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...
  10. 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)...
  11. 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
    ....
  12. 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...
  13. 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...
  14. ncbi Flexibility and variability of TIMP binding: X-ray structure of the complex between collagenase-3/MMP-13 and TIMP-2
    K Maskos
    Max Planck Institut fur Biochemie, Forschungsgruppe Proteinasen, Am Klopferspitz 18, D 82152 Martinsried, Germany
    J Mol Biol 366:1222-31. 2007
    ....
  15. 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)...
  16. ncbi Immunohistochemical study of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 human intervertebral discs
    M Kanemoto
    Department of Orthopaedic Surgery, Shiga University of Medical Science, Japan
    Spine (Phila Pa 1976) 21:1-8. 1996
    ....
  17. ncbi Different mRNA and protein expression of matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases 1 in benign and malignant prostate tissue
    Ralf Lichtinghagen
    Department of Clinical Chemistry, University Medical School, Hannover, Germany
    Eur Urol 42:398-406. 2002
    The aim of this study was to assess the behavior of the matrix metalloproteinases (MMPs) 2 and 9 and the tissue inhibitor of metalloproteinases 1 (TIMP-1) in human prostate cancer.
  18. pmc Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential
    Rita C S Figueira
    Department of Biochemistry, Chemistry Institute, University of Sao Paulo, Sao Paulo, Brazil
    BMC Cancer 9:20. 2009
    ....
  19. 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)...
  20. ncbi Drusen are Cold Spots for Proteolysis: Expression of Matrix Metalloproteinases and Their Tissue Inhibitor Proteins in Age-related Macular Degeneration
    Sergiu T Leu
    Department of Molecular, Cellular and Development Biology, University of California, Santa Barbara, CA 93106, USA
    Exp Eye Res 74:141-54. 2002
    ..The data lead to the speculation that high TIMP-3 concentrations within drusen could inhibit MMPs and as a result slow the proteolytic degradation of these deposits...
  21. 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...
  22. 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...
  23. 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...
  24. 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...
  25. 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...
  26. pmc Extracellular matrix turnover and outflow resistance
    Kate E Keller
    Casey Eye Institute, Oregon Health and Science University, Portland, OR 97239 4197, USA
    Exp Eye Res 88:676-82. 2009
    ..Recently identified podosome- or invadopodia-like structures (PILS) may aid in the focal degradation of ECM and organization of replacement components...
  27. 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...
  28. 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
    ....
  29. pmc Matrix metalloproteinase expression levels suggest distinct enzyme roles during lumbar disc herniation and degeneration
    Beatrice E Bachmeier
    Department of Clinical Chemistry and Clinical Biochemistry, Ludwig Maximilians University Munchen, Munich, Germany
    Eur Spine J 18:1573-86. 2009
    ..Control of the proteolytic activity of MMP-3 may, therefore, come into the focus when aiming to develop new treatment options for early disc degeneration...
  30. 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
    ....
  31. 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
    ....
  32. 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...
  33. 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...
  34. 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...
  35. ncbi Individual Timp deficiencies differentially impact pro-MMP-2 activation
    Jane L English
    Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
    J Biol Chem 281:10337-46. 2006
    ..Thus, TIMP-3 provides an inherent regulation over the kinetics of pro-MMP-2 processing, serving at a level distinct from that of TIMP-2 and TIMP-4...
  36. 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...
  37. ncbi In vitro effects of non-steroidal anti-inflammatory drugs on cytokine, prostanoid and matrix metalloproteinase production by interface membranes from loose hip or knee endoprostheses
    S A Syggelos
    Department of Orthopaedics, School of Medicine, University of Patras, Rio, Patras, Greece
    Osteoarthritis Cartilage 15:531-42. 2007
    ..Involvement of these soluble factors is well documented and probably, a pharmaceutically induced inhibition of them might retard loosening...
  38. 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
    ....
  39. pmc Selective regulation of MMP and TIMP mRNA levels in tree shrew sclera during minus lens compensation and recovery
    John T Siegwart
    Department of Vision Sciences, School of Optometry, University of Alabama at Birmingham, 35294, USA
    Invest Ophthalmol Vis Sci 46:3484-92. 2005
    ....
  40. 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...
  41. 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...
  42. 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 ..
  43. ncbi Plasma TIMP-4 predicts left ventricular remodeling after acute myocardial infarction
    Robin A P Weir
    Cardiology Department, Western Infirmary, Glasgow, Scotland, UK
    J Card Fail 17:465-71. 2011
    ..No relationships have been identified between TIMPs and serial postinfarction change in LV function...
  44. 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...
  45. pmc Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues
    A C P Riddick
    Norfolk and Norwich University Hospital NHS Trust, Norwich NR4 7UY, UK
    Br J Cancer 92:2171-80. 2005
    ....
  46. ncbi Increased expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinases 1 and 2 correlate with poor prognostic variables in renal cell carcinoma
    B V Kallakury
    Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY 12208, USA
    Clin Cancer Res 7:3113-9. 2001
    ..b>Tissue inhibitor of metalloproteinases (TIMPs) inhibit enzymes of the MMP family and preserve stromal integrity, thus inhibiting tumor ..
  47. ncbi Three-dimensional structure of human tissue inhibitor of metalloproteinases-2 at 2.1 A resolution
    A Tuuttila
    Department of Medical Biochemistry and Biophysics Division of Matrix Biology, Karolinska Institutet, Stockholm, S 171 77, Sweden
    J Mol Biol 284:1133-40. 1998
    The three-dimensional structure of human tissue inhibitor of metalloproteinases-2 (TIMP-2) was determined by X-ray crystallography to 2.1 A resolution. The structure of the inhibitor consists of two domains...
  48. ncbi Peroxynitrite inactivates human-tissue inhibitor of metalloproteinase-4
    Sandra Donnini
    Departments of Molecular Biology, University of Siena, Via A Moro, 2, Siena 53100, Italy
    FEBS Lett 582:1135-40. 2008
    ..HPLC/ESI-MS/MS analysis of peroxynitrite-treated TIMP-4 showed modifications at Y114, Y195, Y188 and Y190. In conclusion, TIMP-4 nitration might be a potential mechanism contributing to cardiovascular disease and cancer...
  49. ncbi The role of tissue inhibitors of metalloproteinases in tumorigenesis and metastasis
    William Cruz-Munoz
    Ontario Cancer Institute, University of Toronto, Toronto, Canada
    Crit Rev Clin Lab Sci 45:291-338. 2008
    ....
  50. ncbi Tissue inhibitors of metalloproteinases and programmed cell death: conundrums, controversies and potential implications
    F Mannello
    Istituto di Istologia e Analisi di Laboratorio, Facoltà di Scienze MFN, Universita degli Studi, Urbino, Italy
    Apoptosis 6:479-82. 2001
    ..The aim of this article is to review the exciting and intriguing literature on TIMPs, with special emphasis on their conflicting-paradoxical roles in PCD and their potential clinical usefulness...
  51. 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...
  52. 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...
  53. 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...
  54. 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...
  55. 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...
  56. ncbi 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...
  57. 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
    ....
  58. ncbi 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
    ....
  59. 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...
  60. 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)...
  61. 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
    ....
  62. 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
    ....
  63. 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
    ....
  64. ncbi 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
    ....
  65. 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
    ....
  66. 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
    ....
  67. 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...
  68. 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...
  69. 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...
  70. ncbi Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor
    Seakwoo Lee
    Department of Chemistry and Biochemistry and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA
    Cell Res 16:750-8. 2006
    ..Furthermore, we have found that tissue inhibitor of metalloproteinases-4 (TIMP-4) is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher (p<0...
  71. 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.
  72. ncbi 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...
  73. ncbi Unveiling the surface epitopes that render tissue inhibitor of metalloproteinase-1 inactive against membrane type 1-matrix metalloproteinase
    Meng Huee Lee
    Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Cambridge University, Cambridge CB2 2XY, United Kingdom
    J Biol Chem 278:40224-30. 2003
    ..The enzymatic activity of MT1-MMP is regulated by endogenous inhibitors, the tissue inhibitor of metalloproteinases (TIMP). To date, four variants of mammalian TIMP have been identified...
  74. 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...
  75. ncbi Matrix metalloproteinases in inflammatory bowel disease: boon or a bane?
    Anupama Ravi
    Division of Digestive Diseases, Department of Medicine, Emory University, Atlanta, Georgia, USA
    Inflamm Bowel Dis 13:97-107. 2007
    ..This article focuses on the role of the various MMPs in IBD, discussing their physiologic and pathogenetic role in the context of intestinal defense, mucosal inflammatory response, and immune cell-epithelial interaction...
  76. 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...
  77. 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...
  78. 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...
  79. 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...
  80. 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...
  81. 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...
  82. 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...
  83. 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
    ....
  84. 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...
  85. 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...
  86. 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
    ....
  87. 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
    ....
  88. 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...
  89. ncbi Total conversion of tissue inhibitor of metalloproteinase (TIMP) for specific metalloproteinase targeting: fine-tuning TIMP-4 for optimal inhibition of tumor necrosis factor-{alpha}-converting enzyme
    Meng Huee Lee
    Department of Oncology, Cambridge University, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Cambridge CB2 2XY, United Kingdom
    J Biol Chem 280:15967-75. 2005
    ..Drawing together our previous experience in TACE-targeted mutagenesis by using TIMP-1 and -2 scaffolds, we have finally resolved the mystery of the selective sensitivity of TACE to TIMP-3...
  90. ncbi Differential expression of collagen, MMP, TIMP and fibrogenic-cytokine genes in the granulomatous colon of Schistosoma mansoni-infected mice
    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 100:611-20. 2006
    ..These data indicate that an imbalance in MMP:TIMP expression and enhanced levels of the messages for fibrogenic cytokines underlie the mechanism(s) of the colonic fibrosis seen in mice chronically infected with Schistosoma mansoni...
  91. ncbi Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinase, collagens, and Ki67 antigen in pleural malignant mesothelioma: an immunohistochemical and electron microscopic study
    Hiroshi Hirano
    Department of Pathology, Osaka Medical College, Osaka, Japan
    Med Electron Microsc 35:16-23. 2002
    ..In spite of general agreement that epithelial-type PMM has a better prognosis than other types, there was no significant difference in the Ki67 index among the histological types of PMM...
  92. ncbi Gene polymorphisms related to angiogenesis, inflammation and thrombosis that influence risk for oral cancer
    E Vairaktaris
    Department of Maxillofacial Surgery, University of Athens Medical School, Attikon Hospital, Athens, Greece
    Oral Oncol 45:247-53. 2009
    ..Based on these findings and previous reports, possible interactions of the implicated factors leading to OSCC development, as well as an algorithm of risk estimation are discussed...
  93. ncbi Tissue inhibitor of metalloproteinases-4 inhibits but does not support the activation of gelatinase A via efficient inhibition of membrane type 1-matrix metalloproteinase
    H F Bigg
    Faculty of Dentistry and Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    Cancer Res 61:3610-8. 2001
    ..Hence, TIMP-4 regulates gelatinase A activity by efficient inhibition of MT1-MMP-mediated activation and by inhibiting the activated enzyme and, thus, is a tumor resistance factor in the peritumor stroma...
  94. pmc Differential expression and localization of TIMP-1 and TIMP-4 in human gliomas
    L L Groft
    Department of Biochemistry and Molecular Biology, The University of Calgary, Alberta, Canada
    Br J Cancer 85:55-63. 2001
    ..The differential expression and localization of individual TIMPs may contribute to the pathophysiology of human malignant gliomas, particularly with regard to tumour vascularization...
  95. 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...
  96. ncbi 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, ..
  97. 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...
  98. 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...
  99. 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...
  100. 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...
  101. 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...

Research Grants62

  1. Regulation of Astrocyte TIMP-1 in HIV-Associated Dementia
    JEREL ADAM FIELDS; Fiscal Year: 2011
    ..Our studies will provide a better understanding of the specific mechanistic contributions of activated astrocytes to HIV-1-neuropathogensis and neuroinflammation. ..
  2. New Molecular and Cellular Mechanisms of Glaucoma
    Andrei Surguchov; Fiscal Year: 2013
    ..The purpose of this proposal is to examine how 3-synuclein affects prosurvival/prodeath signaling and how it is implicated in MMP-9 regulation in glaucoma. ..
  3. 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.
  4. Role of Inflammation in the Pathobiology of Abdominal Aortic Aneurysm
    KATHLEEN RAMAN; Fiscal Year: 2013
    ..The clinical relevance of this proposal is underscored by the increasing incidence of AAAs among the VA population and the limited treatment options that are currently available. ..
  5. Homocysteine and Angiotensin II in Renovascular Remodeling
    Utpal Sen; Fiscal Year: 2013
    ..abstract_text> ..
  6. The Role of Leptin in Liver Fibrogenesis
    Frank A Anania; Fiscal Year: 2012
    ....
  7. Neuronal survival, HIV-1 and Astrocyte TIMP-1
    Anuja Ghorpade; Fiscal Year: 2013
    ..Our studies will provide a better understanding of the specific mechanistic contributions of activated astrocytes to HIV-1-neuropathogensis and neuroinflammation. ..
  8. Transforming Growth Factor-beta Signaling Pathways in Thoracic Aortic Aneurysms
    Jeffrey A Jones; Fiscal Year: 2013
    ....
  9. Matrix Metalloproteinases and Spinal Cord Injury
    Linda J Noble; Fiscal Year: 2010
    ....
  10. A novel function of TIMP-1
    Hyeong Reh Choi Kim; Fiscal Year: 2012
    ..by applicant): The long-term objective of this proposal is to unveil the pleiotropic activity of tissue inhibitor of metalloproteinases (TIMP)-1 during breast cancer progression...
  11. Matrix Metalloproteinases in Hepatic Ischemia and Reperfusion Injury
    Ana J Coito; Fiscal Year: 2013
    ..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...
  12. Pathogenesis of Lymphangioleiomyomatosis
    Lucia Schuger; Fiscal Year: 2010
    ..On the contrary, their corresponding inhibitors, tissue inhibitor of metalloproteinases-3 (TIMP-3) and plasminogen activator inhibitor-1 (PAI-1) are downregulated, resulting in an ..
  13. GENETIC ANALYSIS OF SYNAPSE FORMATION AND FUNCTION
    Kendal Broadie; Fiscal Year: 2013
    ....
  14. Factors Released From Embryonic Stem cells and Cardiac Remodeling
    Dinender Kumar Singla; Fiscal Year: 2012
    ..The results from the proposed projects will have long-term implications for future cell- based therapy to treat heart disease (s) using embryonic stem cells or potentially other donor cells. ..
  15. Age-Dependent Mechanisms in Thoracic Aortic Aneurysms
    John S Ikonomidis; Fiscal Year: 2013
    ....
  16. GH Receptor Proteolysis and Shedding
    Stuart J Frank; Fiscal Year: 2013
    ..the metalloprotease TACE (tumor necrosis factor-a cleaving enzyme) and the TACE inhibitor TIMP3 (tissue inhibitor of metalloproteinases-3) that inducibly alters surface GHR availability by proteolytically shedding the receptor ..
  17. Human Cytomegalovirus-Induced Inhibition of Cytotrophoblast Invasion
    CINDY ANNE MORRIS; Fiscal Year: 2012
    ..Defining how HCMV impairs EVT invasion is of major importance to the reproductive community and may provide additional therapeutic targets to maintain viable pregnancy. ..
  18. Spinning Disk Confocoal Microscope
    Judy Drazba; Fiscal Year: 2010
    ..McDonald), and the targeting and trafficking of Smoothened protein, an essential activator in Hedgehog signaling transduction (Dr. Zhu). ..
  19. Endothelial Myocyte Matrix in Cardiac Remodeling
    Suresh C Tyagi; Fiscal Year: 2013
    ..PHS 398/2590 (Rev. 11/07) Page Continuation Format Page ..
  20. 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...
  21. Expression, hormonal regulation and function of microRNA in leiomyoma
    GREGORY SCOTT SCHULTZ; Fiscal Year: 2012
    ..This proposal will investigate how fibroids grow and ways to prevent their symptoms and growth. ..
  22. STRUCTURE, FUNCTION AND APPLICATION OF METALLOPROTEINASE INHIBITORS IN OSTEOARTHR
    Keith Brew; Fiscal Year: 2013
    ..We will investigate the mechanisms through which they act and assess their effectiveness using animal models of the disease and human tissues derived from joint replacement surgery. ..
  23. Sertoli cell injury and mechanisms of testicular germ cell apoptosis
    John H Richburg; Fiscal Year: 2013
    ..In the last aim, experiments are focused on revealing the mechanisms regulating the levels of the c-FLIP protein and its role in altering the sensitivity of germ cell sub-types to undergo FasL-triggered apoptosis. ..
  24. Novel Insights into the Pathogenesis of Light Chain Cardiac Amyloidosis
    Flora Sam; Fiscal Year: 2011
    ....
  25. Mechanisms of Homocysteine-Induced Fibrinogen-Amyloid Plaque Formation
    Suresh C Tyagi; Fiscal Year: 2013
    ..The results of the proposed research should uncover the molecular mechanisms regulating Hcy-Fg-Ab-collagen complex formation and lead to effective strategies for the treatment of cerebrovascular complications during diseases such as AD. ..
  26. Matrix metalloproteinases in Drosophila wound healing
    ANDREA W PAGE-MCCAW; Fiscal Year: 2013
    ..To accomplish these aims we have garnered support from a broad team of experts to inform and guide our experiments. ..
  27. Risk factors for site-specific metastasis in esophageal cancer
    JULIAN ABRAMS; Fiscal Year: 2012
    ....
  28. Mechanisms of Reduced Fecundity in Endometriosis: A role for MMPs and TIMPs
    KATHY L TIMMS; Fiscal Year: 2012
    ..abstract_text> ..
  29. METALLOPROTEINASES IN TUMOR NEOVASCULARIZATION
    Alex Y Strongin; Fiscal Year: 2013
    ..Precise analysis of the MT1-MMP functionality will pave the way for rational design of inhibitory molecules directed against its specific enzymatic and non-enzymatic functions. ..
  30. Aortic Aneurysm Formation: Mechanisms of Oxidative Stress-Induced MMP Expression
    MATTHEW JEREMIAH EAGLETON; Fiscal Year: 2012
    ..A better understanding of the pathogenesis of AAA formation could lead to the development of pharmacotherapies used to prevent aneurysm expansion and rupture. ..
  31. Spinal Matrix Metalloproteinases in Hyperalgesia and Allodynia
    CHRISTINA CHRISTIANSON; Fiscal Year: 2010
    ..Many chronic pain conditions are inadequately alleviated by available medications. This proposal will examine the role of matrix metalloproteinases in the onset and the duration of pain sensations. ..
  32. Untangling Amyloid Plaques With Proteases
    Jin Moo Lee; Fiscal Year: 2010
    ..If the hypothesis is true, potential targets for intervention to degrade plaques may be identified. ..
  33. Development of a conditional T1MP-1 knockout mouse
    Stephen J Crocker; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a pleiotrophic extracellular protein that is dramatically upregulated in the brain following inflammation or injury...
  34. Mitophagic and anti-angiogenic mechanism of heart failure
    Suresh C Tyagi; Fiscal Year: 2013
    ..The positive outcome of this project will have therapeutic ramifications for chronic heart failure. ..
  35. Crevicular Fluid Content During Early Wound Healing- Implant versus Tooth
    Binnaz Leblebicioglu; Fiscal Year: 2010
    ..This model will allow investigation of early stages of wound healing prior to soft tissue seal maturation without altering actual treatment protocol. ..
  36. NON-PROTEOLYTIC INTERACTIONS OF TIMP-2 AND MT1-MMP
    Paolo Mignatti; Fiscal Year: 2013
    ..a short cytoplasmic tail, forms a stoichiometric complex with its physiological protein inhibitor, tissue inhibitor of metalloproteinases-2 (TIMP-2)...
  37. Bacteria in Lower Airways and Airway Inflammation in Children with Asthma
    PIA JOHANNA HAUK; Fiscal Year: 2013
    ..The percentages of BAL neutrophils correlated with metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1 and MMP-9/TIMP-1 ratio, indicating that presence of endotoxin through presence of Gram-..
  38. Cognitive Function in SLE (COGNITION)
    Robin L Brey; Fiscal Year: 2010
    ..The information that will be gained from this study is essential for the successful discovery of biological processes that impact on cognitive function in SLE that could be potentially amenable to disease-reversing therapies. ..
  39. Molecular insights into the pathogenesis of Sorsby Fundus Dystrophy
    Jian Hua Qi; Fiscal Year: 2013
    ..Undoubtedly, this would provide novel insights into the pathogenesis of SFD and ARMD that share similar disease phenotype, and thereby establish a potential therapeutic target for these ocular diseases. ..
  40. Localized Targeting of Matrix Proteases Following Myocardial Infarction
    Francis G Spinale; Fiscal Year: 2013
    ..This study will validate a novel therapeuti intervention to control MMPs following a heart attack and thereby develop innovative treatments to prevent progressive myocardial remodeling in patients after a heart attack. ..
  41. 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...
  42. Invasive breast cancer with and without DCIS: Race, risk factors and outcomes
    PATRICIA ANN MASSO-WELCH; Fiscal Year: 2013
    ....
  43. Role of TIMP-3 in Ocular Neovascularization
    Bela Anand Apte; Fiscal Year: 2009
    ..Mutations in the Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) gene cause SFD...
  44. 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. ..
  45. PA/PLASMIN/GELATINASE CASCADE IN DIABETIC NEPHROPATHY
    WILLIAM BARICOS; Fiscal Year: 2000
    ....
  46. Pericyte Proteinase Inhibitors and EC Tube Stabilization
    George E Davis; Fiscal Year: 2013
    ....
  47. Role of Inflammatory Neutrophils and their Unique MMP-9 in Tumor Progression
    James P Quigley; Fiscal Year: 2013
    ..The results will be then validated in a number of murine models of angiogenesis and metastasis including orthotopic transplants and transgenic models focusing on the human disease-like TRAMP model. ..
  48. The MMP system in human ovulation: localization, regulation, and function
    Thomas E Curry; Fiscal Year: 2013
    ....
  49. 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 ..
  50. EXTRACELLULAR MATRIX DEGRADATION IN SKIN
    George Stricklin; Fiscal Year: 1993
    ..These degradative enzymes are in turn regulated by a proteinase inhibitor, Tissue Inhibitor of MetalloProteinases or TIMP...
  51. 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. ..
  52. REGULATION OF CELL MIGRATION IN VASCULAR REMODELING
    Eric Howard; Fiscal Year: 2002
    ..Understanding this mechanism will be important in defining the biochemical events that occur during vascular remodeling in both normal and disease processes. ..
  53. METALLOPROTEINASES AND OVARIAN FUNCTION
    Thomas Curry; Fiscal Year: 1999
    ....
  54. Sequencing by Recognition
    Stuart Lindsay; Fiscal Year: 2009
    ..We will collaborate with the Timp Laboratory (University of Illinois, Urbana- Champaign) in order to tie our designs to the materials constraints of the solid state nanopores being developed there. ..
  55. NOVEL ROLE AND REGULATION OF UTERINE TIMPS
    Warren Nothnick; Fiscal Year: 2000
    ..abstract_text> ..
  56. REGULATION OF RETINAL NEOVASCULARIZATION BY TIMP3
    Bela Anand Apte; Fiscal Year: 2002
    ..The broad long term goal of this proposal is to gain an understanding of the mechanism(s) by which alterations in matrix integrity may regulate retinal neovascularization using TIMP-3 mutations in SFD as a model. ..
  57. PATHOGENESIS OF RETINAL DEGENERATIONS
    Samuel Jacobson; Fiscal Year: 2001
    ..SFD, was caused by mutations in the gene encoding an extracellular matrix molecule known as tissue inhibitor of metalloproteinases-3 (TIMP-3)...
  58. Ventricular Matrix Remodeling: Correlates and Prognosis
    Vasan Ramachandran; Fiscal Year: 2004
    ..The proposed translational research will likely yield seminal information that could directly improve our efforts to prevent CHF through the biochemical assessment of cardiac ECM remodeling. ..
  59. ENDOGENOUS INHIBITORS OF ADAMS/MDC PROTEINASES
    Jay Fox; Fiscal Year: 2001
    ..Isolation and characterization of these inhibits could therefore be of future importance in developing novel pharmacological agents for the regulation of ADAMs proteins' functions in pathological states. ..
  60. MOLECULAR MECHANISMS OF ANEURYSMAL DEGENERATION
    Robert Thompson; Fiscal Year: 2009
    ..Taken together, these studies will contribute important new information on the mechanisms underlying extracellular matrix degradation in aneurysmal degeneration. ..
  61. PATHOGENESIS OF RADIATION-INDUCED KIDNEY INJURY
    Michael Robbins; Fiscal Year: 2004
    ..other ROS generators in vitro leads to modulation of plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinases-2 (TIMP-2) matrix metalloproteinase-2 (MMP-2), TGF-B and angiotensinogen (AGT, precursor of Ang II)..
  62. Role of TIMPs in Hematopoietic Stem Cell Biology
    KEVIN BUNTING; Fiscal Year: 2006
    ....