Timp2

Summary

Gene Symbol: Timp2
Description: tissue inhibitor of metalloproteinase 2
Alias: D11Bwg1104e, Timp-2, metalloproteinase inhibitor 2, tissue inhibitor of metalloproteinases 2
Species: mouse

Top Publications

  1. pmc Tissue inhibitor of metalloproteinase-2 promotes neuronal differentiation by acting as an anti-mitogenic signal
    Leonor Perez-Martinez
    Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA
    J Neurosci 25:4917-29. 2005
  2. doi Tissue inhibitor of metalloproteinases protect blood-brain barrier disruption in focal cerebral ischemia
    Motoaki Fujimoto
    Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    J Cereb Blood Flow Metab 28:1674-85. 2008
  3. doi TIMP2 deficient mice develop accelerated osteoarthritis via promotion of angiogenesis upon destabilization of the medial meniscus
    Meng Mi
    Department of Orthopedics, Second Xiangya Hospital, Central South University, Changsha, Hunan Province 410011, PR China
    Biochem Biophys Res Commun 423:366-72. 2012
  4. ncbi Differential regulation of MMP-9 and TIMP-2 expression in malignant melanoma developed in metallothionein/RET transgenic mice
    M Asai
    Department of Pathology, Nagoya University School of Medicine
    Jpn J Cancer Res 90:86-92. 1999
  5. ncbi Expression of the type IV collagenase system during mouse kidney development and tubule segmentation
    B Legallicier
    INSERM U489, Tenon Hospital and St Antoine Medical Faculty, Paris 6 University, Paris, France
    J Am Soc Nephrol 12:2358-69. 2001
  6. ncbi Urinary matrix metalloproteinases and their endogenous inhibitors predict hepatic regeneration after murine partial hepatectomy
    Arin K Greene
    Department of Surgery and the Vascular Biology Program, Children s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
    Transplantation 78:1139-44. 2004
  7. ncbi Prepulse inhibition and fear-potentiated startle are altered in tissue inhibitor of metalloproteinase-2 (TIMP-2) knockout mice
    Diane M Jaworski
    Department of Anatomy and Neurobiology, University of Vermont College of Medicine, 149 Beaumont Avenue, HSRF 418, Burlington, VT 05405, USA
    Brain Res 1051:81-9. 2005
  8. pmc Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates myogenesis and beta1 integrin expression in vitro
    Gentian Lluri
    Department of Anatomy and Neurobiology, University of Vermont College of Medicine, 149 Beaumont Ave, HSRF 418, Burlington, VT 05405, USA
    Exp Cell Res 314:11-24. 2008
  9. doi Ascorbate-induced osteoblast differentiation recruits distinct MMP-inhibitors: RECK and TIMP-2
    Willian F Zambuzzi
    Departamento de Bioquimica, Instituto de Biologia, Universidade Estadual de Campinas UNICAMP, Cidade Universitaria, 13083 970, Campinas, Sao Paulo, Brazil
    Mol Cell Biochem 322:143-50. 2009
  10. doi Ontogeny of MMPs and TIMPs in the murine neocortex
    Nathalie Bednarek
    INSERM, U676, Paris 75019, France
    Pediatr Res 65:296-300. 2009

Research Grants

  1. Molecular Regulation of TIMP-2 in Neuron Cell Cycle
    DIANE JAWORSKI; Fiscal Year: 2007
  2. EPITHELIAL/MESENCHYMAL INTERACTIONS IN LUNG DEVELOPMENT
    Farrah Kheradmand; Fiscal Year: 2002
  3. Mast Cell Role in Masseter Muscle Repair
    JOYCE MORRIS WIMAN; Fiscal Year: 2005
  4. The Role of TIMP-1 in Uterine Physiology
    Warren Nothnick; Fiscal Year: 2005
  5. The Role of Proteinases in Experimental Asthma
    Farrah Kheradmand; Fiscal Year: 2006
  6. The Role of Proteases in Lung Inflammation & Remodeling
    Farrah Kheradmand; Fiscal Year: 2007
  7. Estrogen regulation of uterine microRNAs: Novel factors in MMP-9 regulation
    Warren Nothnick; Fiscal Year: 2008
  8. Viral-induced T Cell Responses in COPD Exacerbation
    Farrah Kheradmand; Fiscal Year: 2009
  9. Immune modulators of inflammation in servere COPD
    Farrah Kheradmand; Fiscal Year: 2010

Scientific Experts

Detail Information

Publications96

  1. pmc Tissue inhibitor of metalloproteinase-2 promotes neuronal differentiation by acting as an anti-mitogenic signal
    Leonor Perez-Martinez
    Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA
    J Neurosci 25:4917-29. 2005
    ....
  2. doi Tissue inhibitor of metalloproteinases protect blood-brain barrier disruption in focal cerebral ischemia
    Motoaki Fujimoto
    Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    J Cereb Blood Flow Metab 28:1674-85. 2008
    ..These results suggest that TIMP-1 inhibits MMP-9 activity and can play a neuroprotective role in cerebral ischemia...
  3. doi TIMP2 deficient mice develop accelerated osteoarthritis via promotion of angiogenesis upon destabilization of the medial meniscus
    Meng Mi
    Department of Orthopedics, Second Xiangya Hospital, Central South University, Changsha, Hunan Province 410011, PR China
    Biochem Biophys Res Commun 423:366-72. 2012
    ..In this study, we demonstrated that the expression of tissue inhibitor of metalloproteinases-2 (TIMP2), an anti-angiogenic factor, was present at high levels in normal articular chondrocytes, and was drastically ..
  4. ncbi Differential regulation of MMP-9 and TIMP-2 expression in malignant melanoma developed in metallothionein/RET transgenic mice
    M Asai
    Department of Pathology, Nagoya University School of Medicine
    Jpn J Cancer Res 90:86-92. 1999
    ....
  5. ncbi Expression of the type IV collagenase system during mouse kidney development and tubule segmentation
    B Legallicier
    INSERM U489, Tenon Hospital and St Antoine Medical Faculty, Paris 6 University, Paris, France
    J Am Soc Nephrol 12:2358-69. 2001
    ..MMP2) and MMP9 and their related proteins, MT1-MMP, tissue inhibitor of metalloproteinases 1 (TIMP1), TIMP2, and TIMP3, are expressed during kidney morphogenesis and nephrogenesis, but the renal ontogeny of these proteins ..
  6. ncbi Urinary matrix metalloproteinases and their endogenous inhibitors predict hepatic regeneration after murine partial hepatectomy
    Arin K Greene
    Department of Surgery and the Vascular Biology Program, Children s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
    Transplantation 78:1139-44. 2004
    ..We therefore hypothesized that urinary MMPs and their endogenous tissue inhibitors of matrix metalloproteinases (TIMPs) might also provide important information regarding initiation and progression of liver regeneration...
  7. ncbi Prepulse inhibition and fear-potentiated startle are altered in tissue inhibitor of metalloproteinase-2 (TIMP-2) knockout mice
    Diane M Jaworski
    Department of Anatomy and Neurobiology, University of Vermont College of Medicine, 149 Beaumont Avenue, HSRF 418, Burlington, VT 05405, USA
    Brain Res 1051:81-9. 2005
    ..This is the first report of a phenotype for the TIMP-2(-/-) mice and suggests that TIMP-2 may play a role in the synaptic plasticity underlying learning and memory...
  8. pmc Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates myogenesis and beta1 integrin expression in vitro
    Gentian Lluri
    Department of Anatomy and Neurobiology, University of Vermont College of Medicine, 149 Beaumont Ave, HSRF 418, Burlington, VT 05405, USA
    Exp Cell Res 314:11-24. 2008
    ..Elucidating the role of TIMP-2 in myogenesis in vitro may lead to new therapeutic options for the use of TIMP-2 in myopathies and muscular dystrophies in vivo...
  9. doi Ascorbate-induced osteoblast differentiation recruits distinct MMP-inhibitors: RECK and TIMP-2
    Willian F Zambuzzi
    Departamento de Bioquimica, Instituto de Biologia, Universidade Estadual de Campinas UNICAMP, Cidade Universitaria, 13083 970, Campinas, Sao Paulo, Brazil
    Mol Cell Biochem 322:143-50. 2009
    ....
  10. doi Ontogeny of MMPs and TIMPs in the murine neocortex
    Nathalie Bednarek
    INSERM, U676, Paris 75019, France
    Pediatr Res 65:296-300. 2009
    ..No gender effect was observed on any of the study parameters. This comprehensive study will serve as a basis for future investigations into the role for MMPs and TIMPs in normal brain development and prenatal brain injury...
  11. pmc A dual role for microglia in promoting tissue inhibitor of metalloproteinase (TIMP) expression in glial cells in response to neuroinflammatory stimuli
    Jennifer V Welser-Alves
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Neuroinflammation 8:61. 2011
    ..As such, it is important to define the TIMP expression profile in these cells, as well as the mechanisms of regulation by neuroinflammatory stimuli...
  12. pmc Differential effects of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 on atherosclerosis and monocyte/macrophage invasion
    Karina Di Gregoli
    School of Clinical Sciences, University of Bristol, Level 7, Bristol Royal Infirmary, Bristol BS2 8HW, UK
    Cardiovasc Res 109:318-30. 2016
    ..We therefore investigated the impact of TIMP-1 and TIMP-2 knockout on atherosclerotic plaque burden and composition in apolipoprotein E-knockout (Apoe(-/-)) mice and studied the underlying effects on monocyte/macrophage behaviour...
  13. doi TIMP3 is the primary TIMP to regulate agonist-induced vascular remodelling and hypertension
    Ratnadeep Basu
    Department of Physiology, University of Alberta, 474 HMRC, Edmonton, Alberta, Canada T6G 2S2
    Cardiovasc Res 98:360-71. 2013
    ..In response to a hypertensive stimulus, the balance between MMPs and TIMPs is altered. We examined the role of TIMPs in agonist-induced hypertension...
  14. doi TIMP2 and TIMP3 have divergent roles in early renal tubulointerstitial injury
    Zuocheng Wang
    1 Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada 2 Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
    Kidney Int 85:82-93. 2014
    ..Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of matrix metalloproteinases (MMPs). While TIMP2 and TIMP3 inhibit MMPs, TIMP3 also inhibits activation of pro-MMP2, whereas TIMP2 promotes it...
  15. pmc Retinal MMP-12, MMP-13, TIMP-1, and TIMP-2 expression in murine experimental retinal detachment
    Bongsu Kim
    Havener Eye Institute, Department of Ophthalmology and Visual Science, The Ohio State University, Columbus, Ohio, United States
    Invest Ophthalmol Vis Sci 55:2031-40. 2014
    ..The purpose of this study was to investigate the retinal expression of select MMPs, including MMP-12, MMP-13, and associated inhibitors in a murine model of retinal detachment...
  16. doi Differential role of TIMP2 and TIMP3 in cardiac hypertrophy, fibrosis, and diastolic dysfunction
    Dong Fan
    Department of Physiology Cardiovascular research Centre, Mazankowski Alberta Heart Institute
    Cardiovasc Res 103:268-80. 2014
    ..We investigated the impact of TIMP2 vs. TIMP3 deficiency in angiotensin II (Ang II)-induced myocardial remodelling and cardiac dysfunction.
  17. pmc Overexpression of miR-483-5p/3p cooperate to inhibit mouse liver fibrosis by suppressing the TGF-β stimulated HSCs in transgenic mice
    Fuyuan Li
    Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China
    J Cell Mol Med 18:966-74. 2014
    ..Our work identifies the pathway that regulates liver fibrosis by inhibiting the activation of HSCs. ..
  18. pmc Effects of reduced β2-glycoprotein I on the expression of aortic matrix metalloproteinases and tissue inhibitor matrix metalloproteinases in diabetic mice
    Jun Xu
    2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, The Key Laboratory of Hormones and Development Ministry of Health, Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, NO, 66 Tong An Road, Heping District, Tianjin, 300070, China
    BMC Cardiovasc Disord 14:114. 2014
    ..We investigated the effects of reduced β(2)GP I on the expression of various matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the aortas of diabetic mice...
  19. pmc Timp3 deficient mice show resistance to developing breast cancer
    Hartland W Jackson
    Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada
    PLoS ONE 10:e0120107. 2015
    ..Together our data is the first to identify a tumor promoting role of endogenous Timp3 in vivo, the spatial and temporal windows of this effect, and its dependence on Tnfr1. ..
  20. doi Low-dose UVB irradiation prevents MMP2-induced skin hyperplasia by inhibiting inflammation and ROS
    Lin Dang
    Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P R China
    Oncol Rep 34:1478-86. 2015
    ..Further investigation of MMP2 inhibitors of TIMP2/TIMP4 showed an upregulated TIMP2 expression, but not TIMP4...
  21. pmc Targeting Interleukin-1β Reduces Leukocyte Production After Acute Myocardial Infarction
    Hendrik B Sager
    From Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, MA H B S, T H, M H, P D, G C, M S, G R W, B T, Y I, Y S, R W, F K S, M N Department of Systems Biology, Harvard Medical School, Boston, MA R W and Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Boston, MA P L
    Circulation 132:1880-90. 2015
    ..MI-associated blood leukocytosis correlates inversely with patient survival, yet the signals driving heightened leukocyte production after MI remain incompletely understood...
  22. ncbi Linkage analysis demonstrates that the Timp-2 locus is on mouse chromosome 11
    W G Stetler-Stevenson
    Tumor Invasion and Metastasis Section, National Cancer Institute, Bethesda, Maryland 20892
    Genomics 14:828-9. 1992
  23. pmc Tissue inhibitor of metalloproteinases-2 is expressed in the interstitial matrix in adult mouse organs and during embryonic development
    L Blavier
    Division of Hematology Oncology, Childrens Hospital Los Angeles, California 90027, USA
    Mol Biol Cell 8:1513-27. 1997
    ..The pattern of expression significantly differs from that observed with TIMP-1 and TIMP-3, therefore, suggesting specific roles for each inhibitor during tissue remodeling and development...
  24. ncbi [Experimental study on extracts from ginseng, notoginseng and chuanxiong for delaying vascular aging in senescent mice]
    Yan Lei
    Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing
    Zhongguo Zhong Xi Yi Jie He Za Zhi 30:946-51. 2010
    ..To explore the vascular structural and functional change in aged mice, and the intervention roles of extracts from ginseng, notoginseng and chuanxiong (Exs) on it...
  25. doi Lack of tissue inhibitor of metalloproteinases 2 leads to exacerbated left ventricular dysfunction and adverse extracellular matrix remodeling in response to biomechanical stress
    Vijay Kandalam
    Assistant Professor, Department of Physiology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada
    Circulation 124:2094-105. 2011
    ..b>Tissue inhibitor of metalloproteinases 2 is unique among TIMPs in activating pro-MMP2 in addition to inhibiting a number of MMPs...
  26. ncbi Tissue inhibitors of matrix metalloproteinases 1 and 2 and matrix metalloproteinase activity in the serum and lungs of mice with lewis lung carcinoma
    Ya A Kisarova
    Institute of Physiology, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk
    Bull Exp Biol Med 153:874-7. 2012
    ..Increased concentration of TIMP-2 in the lungs (but not in the serum) can be regarded as an indicator of Lewis lung carcinoma metastasizing...
  27. doi The matrix metalloproteinase inhibitor marimastat promotes neural progenitor cell differentiation into neurons by gelatinase-independent TIMP-2-dependent mechanisms
    Maddalena Sinno
    Department of Biology and Biotechnology Charles Darwin, Sapienza, University of Rome, Rome, Italy
    Stem Cells Dev 22:345-58. 2013
    ....
  28. doi Thymic alterations induced by Plasmodium berghei: expression of matrix metalloproteinases and their tissue inhibitors
    Alliny Carolina Dionete Lima
    Department of Structural and Functional Biology, University of Campinas UNICAMP, Campinas, Sao Paulo, Brazil
    Cell Immunol 279:53-9. 2012
    ..Also, the presence of active MMP-2 was detected. These data are suggestive of MMPs and TIMPs importance in the earlier observed changes in the extracellular matrix during thymic alterations after plasmodium infection...
  29. doi TIMP2 deficiency accelerates adverse post-myocardial infarction remodeling because of enhanced MT1-MMP activity despite lack of MMP2 activation
    Vijay Kandalam
    Department of Physiology, Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada
    Circ Res 106:796-808. 2010
    ..b>TIMP2 is highly expressed in the heart and is the only TIMP that, in addition to inhibiting MMPs, is required for cell ..
  30. pmc Sexually dimorphic diet-induced insulin resistance in obese tissue inhibitor of metalloproteinase-2 (TIMP-2)-deficient mice
    Diane M Jaworski
    Department of Anatomy and Neurobiology, University of Vermont College of Medicine, 149 Beaumont Avenue, HSRF 418, Burlington, Vermont 05405, USA
    Endocrinology 152:1300-13. 2011
    ....
  31. pmc Secreted versus membrane-anchored collagenases: relative roles in fibroblast-dependent collagenolysis and invasion
    Farideh Sabeh
    Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 284:23001-11. 2009
    ..Hence, whereas secreted collagenases arm fibroblasts with potent matrix-resorptive activity, only MT1-MMP confers the focal collagenolytic activity necessary for supporting the tissue-invasive phenotype...
  32. pmc Endothelial cell lumen and vascular guidance tunnel formation requires MT1-MMP-dependent proteolysis in 3-dimensional collagen matrices
    Amber N Stratman
    Department of Medical Pharmacology and Physiology, School of Medicine, Dalton Cardiovascular Center, University of Missouri Columbia, MO 65212, USA
    Blood 114:237-47. 2009
    ..In summary, a fundamental and previously unrecognized purpose of EC tube morphogenesis is to create networks of matrix conduits that are necessary for EC migration and tube remodeling events critical to blood vessel assembly...
  33. pmc uPARAP expression during murine lung development
    Leah Smith
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Harborview Medical Center, University of Washington, Box 359640, 325 9th Ave, Seattle, WA 98104, USA
    Gene Expr Patterns 8:486-93. 2008
    ..Finally, we compared lung development between wild-type and uPARAP(-/-) mice, and found no significant histologic differences, indicating the presence of alternative collagen degradation pathways during murine lung development...
  34. doi Increased glomerular matrix metalloproteinase activity in murine lupus nephritis
    Anders A Tveita
    1Department of Biochemistry, Institute of Medical Biology, University of Tromsø, Tromsø, Norway
    Kidney Int 74:1150-8. 2008
    ..When proteinuria appeared we found an increased net glomerular gelatinolytic activity. These studies suggest that matrix metalloproteinases contribute to extracellular matrix expansion and proteinuria by altering matrix composition...
  35. ncbi Temporal and spatial expression of tissue inhibitors of metalloproteinases during the natural ovulatory cycle of the mouse
    D S Inderdeo
    Department of Biochemistry, University of Western Ontario, London, Canada
    Biol Reprod 55:498-508. 1996
    ..We propose that in the natural ovulatory process, TIMP-1 is probably a factor that regulates corpus luteum regression while TIMP-3 is important in maintaining the structural integrity of the corpus luteum...
  36. pmc Overexpression of delta-like 4 induces arterialization and attenuates vessel formation in developing mouse embryos
    Alexandre Trindade
    Centro de Informatica do Instituto Superior de Agronomia CIISA, Lisbon Technical University, Lisbon, Portugal
    Blood 112:1720-9. 2008
    ..These results establish the role of Dll4 in arterial identity determination, and regulation of angiogenesis subject to dose and location...
  37. ncbi Matrix metalloproteinases and TIMPS in cultured C57BL/6J-cpk kidney tubules
    C A Rankin
    Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, USA
    Kidney Int 50:835-44. 1996
    ..These data suggest that cystic kidney tubules synthesize and secrete high levels of MMPs which may then participate in the restructuring of the tubular basement membrane...
  38. ncbi Association of TIMP-2 with extracellular matrix exposed to mechanical stress and its co-distribution with periostin during mouse mandible development
    Nagako Yoshiba
    Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
    Cell Tissue Res 330:133-45. 2007
    ..We suggest that TIMP-2 and periostin are co-distributed on ECM exposed to mechanical forces and coordinately function as ECM modulators...
  39. ncbi Role of TIMP-1 and TIMP-2 in the progression of cerebral aneurysms
    Tomohiro Aoki
    Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kawaharacho, Shogoin, Sakyo ku, Kyoto, Japan
    Stroke 38:2337-45. 2007
    ..We investigated the role of TIMPs in the progression of cerebral aneurysms in the present study...
  40. pmc Potential regulatory relationship between the nested gene DDC8 and its host gene tissue inhibitor of metalloproteinase-2
    Diane M Jaworski
    Departments of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA
    Physiol Genomics 28:168-78. 2007
    ..That TIMP-2 transcripts in wild-type brain contain DDC8 sequence suggests alternative splicing between the two genes...
  41. pmc Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates neuromuscular junction development via a beta1 integrin-mediated mechanism
    Gentian Lluri
    Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA
    J Neurobiol 66:1365-77. 2006
    ..Given that fast-twitch fibers are lost in muscular dystrophies and age-related sarcopenia, if TIMP-2 regulates mechanotransduction in an MMP-independent manner it opens new potential therapeutic avenues...
  42. ncbi Intact vitronectin induces matrix metalloproteinase-2 and tissue inhibitor of metalloproteinases-2 expression and enhanced cellular invasion by melanoma cells
    L M Bafetti
    Department of Obstetrics and Gynecology, Northwestern University Medical School, Chicago, Illinois 60611, USA
    J Biol Chem 273:143-9. 1998
    ..Together, these data provide evidence for a functional link between adhesion and proteolysis and suggest a potential mechanism whereby adhesion of an invasive cell to the extracellular matrix regulates subsequent invasive behavior...
  43. pmc Opposing roles of PARP-1 in MMP-9 and TIMP-2 expression and mast cell degranulation in dyslipidemic dilated cardiomyopathy
    Chetan P Hans
    Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA, USA
    Cardiovasc Pathol 20:e57-68. 2011
    ....
  44. pmc Functional genomics complements quantitative genetics in identifying disease-gene associations
    Yuanfang Guan
    Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA
    PLoS Comput Biol 6:e1000991. 2010
    ..predictions (not observed in any previous GWAS/QTL studies) and found significant bone density defects for both Timp2 and Abcg8 deficient mice...
  45. ncbi Tissue inhibitor of metalloproteinase-2 inhibits T-cell infiltration and preserves pancreatic beta-cell function in an in vitro type 1 diabetes mellitus model
    Chris C Woods
    Department of Microbiology and Immunology, University of Arizona College of Medicine, 1501 N Campbell Avenue, Tuscon, 85724, USA
    J Autoimmun 27:28-37. 2006
    ..Our findings suggest that TIMP-2 is effective at blocking infiltration of autoreactive T-cells into target pancreas tissue thereby preserving pancreatic beta-cell mass...
  46. ncbi Overexpression of tissue inhibitor of metalloproteinases-2 retroviral-mediated gene transfer in vivo inhibits tumor growth and invasion
    S Imren
    Division of Hematology Oncology, University of Southern California, Los Angeles 90027, USA
    Cancer Res 56:2891-5. 1996
    ....
  47. ncbi Epigenetic characterization of the PBEF and TIMP-2 genes in the developing placentae of normal mice
    Hong Rye Kim
    Department of Animal Science and Biotechnology, Research Center for Transgenic Cloned Pig, Chungnam National University, Deajeon, Korea
    BMB Rep 44:535-40. 2011
    ....
  48. pmc ATXN1 protein family and CIC regulate extracellular matrix remodeling and lung alveolarization
    Yoontae Lee
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Dev Cell 21:746-57. 2011
    ..These findings demonstrate a critical role of ATXN1/ATXN1L-CIC complexes in extracellular matrix (ECM) remodeling during development and their potential roles in pathogenesis of disorders affecting ECM remodeling...
  49. ncbi Temporal expression of tissue inhibitors of metalloproteinases in mouse reproductive tissues during gestation
    P Waterhouse
    Department of Biochemistry, University of Western Ontario, London, Canada
    Mol Reprod Dev 35:219-26. 1993
    ..abstract truncated at 250 words)..
  50. ncbi Solution structure of the active domain of tissue inhibitor of metalloproteinases-2. A new member of the OB fold protein family
    R A Williamson
    Research School of Biosciences, Biological Laboratory, University of Kent, Canterbury, U K
    Biochemistry 33:11745-59. 1994
    ..Furthermore, the structure has revealed conserved surface regions of potential functional importance...
  51. ncbi Expression of interstitial collagenase is restricted to skeletal tissue during mouse embryogenesis
    V Mattot
    CNRS URA 1160, Institut Pasteur, Lille, France
    J Cell Sci 108:529-35. 1995
    ....
  52. ncbi 92-kDa type IV collagenase and TIMP-3, but not 72-kDa type IV collagenase or TIMP-1 or TIMP-2, are highly expressed during mouse embryo implantation
    P Reponen
    Biocenter Oulu, University of Oulu, Finland
    Dev Dyn 202:388-96. 1995
    ..The results suggest a central role for 92 kDa type IV collagenase and TIMP-3 in the extracellular proteolysis associated with implantation of the early embryo...
  53. ncbi Mouse Cd7 maps to chromosome 11
    D M Lee
    Department of Microbiology, Duke University Medical Center, Durham, NC 27710
    Immunogenetics 39:289-90. 1994
  54. ncbi Determination of tissue inhibitor of metalloproteinases-2 (TIMP-2) in experimental animals using monoclonal antibodies against TIMP-2-specific oligopeptides
    N Fujimoto
    Research Laboratories I, Fuji Chemical Industries, Ltd, Toyama, Japan
    J Immunol Methods 187:33-9. 1995
    ..Using human TIMP-2 as a standard, TIMP-2 levels in the sera of mouse, rat, guinea pig and rabbit were approximately 80, 200, 270 and 25 ng/ml, respectively...
  55. ncbi Differential regulation of TIMP-1 and TIMP-2 mRNA expression in normal and Ha-ras-transformed murine fibroblasts
    K J Leco
    Department of Pharmacology and Therapeutics, University of Calgary, Alberta, Canada
    Gene 117:209-17. 1992
    ..Our data demonstrate that the mechanisms that regulate murine TIMP-1 and TIMP-2 expression are distinct arguing for different physiological roles for the two TIMPs...
  56. ncbi Cloning and sequencing of the cDNA encoding a mouse tissue inhibitor of metalloproteinase-2
    S Shimizu
    Pathophysiology Unit, Aichi Cancer Center Research Institute, Nagoya, Japan
    Gene 114:291-2. 1992
    ..While high homology was observed with the sequences encoding the human (hTIMP-2) and bovine (bTIMP-2) genes, mTIMP-2 contained a long 3'-nontranslated region not observed in the hTIMP-2 or bTIMP-2 genes...
  57. ncbi The gene for tissue inhibitor of metalloproteinases-2 is localized on human chromosome arm 17q25
    Y De Clerck
    Department of Pediatrics, Childrens Hospital of Los Angeles, California
    Genomics 14:782-4. 1992
    Tissue inhibitor of metalloproteinases-2 (TIMP2) is a natural inhibitor of several proteinases that are involved in the degradation of the extracellular matrix...
  58. pmc TIMP-2 is required for efficient activation of proMMP-2 in vivo
    Z Wang
    Roswell Park Cancer Institute, Department of Molecular and Cellular Biology, Buffalo, New York 16263, USA
    J Biol Chem 275:26411-5. 2000
    ..Mutant mice were overtly normal, viable, and fertile on the C57BL/6 background, indicating that both TIMP-2 and activated proMMP-2 are dispensable for normal development...
  59. ncbi Matrix metalloproteinases regulate mesonephric cell migration in developing XY gonads which correlates with the inhibition of tissue inhibitor of metalloproteinase-3 by Sry
    Koichiro Nishino
    Laboratory of Applied Genetics, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1 1 1, Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
    Dev Growth Differ 44:35-43. 2002
    ..These findings are an important clue for the elucidation of testicular formation in developing gonads...
  60. pmc Signaling through the EGF receptor controls lung morphogenesis in part by regulating MT1-MMP-mediated activation of gelatinase A/MMP2
    Farrah Kheradmand
    Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
    J Cell Sci 115:839-48. 2002
    ..MT1-MMP is, in turn, necessary for activation of MMP-2, a mesenchymal enzyme that is required for normal lung morphogenesis...
  61. ncbi Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in the mouse uterus during the peri-implantation period
    S K Das
    Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City 66160, USA
    Dev Genet 21:44-54. 1997
    ....
  62. pmc TGF-beta3-induced palatogenesis requires matrix metalloproteinases
    L Blavier
    Division of Hematology Oncology, Department of Pediatrics, Childrens Hospital Los Angeles and the Keck School of Medicine of the University of Southern California, Los Angeles, California 90027, USA
    Mol Biol Cell 12:1457-66. 2001
    ..Our observations indicate for the first time that the proteolytic degradation of the ECM by MMPs is a necessary step for palatal fusion...
  63. ncbi A molecular analysis of matrix remodeling and angiogenesis during long bone development
    C I Colnot
    Department of Orthopedic Surgery, University of California at San Francisco, CA 94143 0514, USA
    Mech Dev 100:245-50. 2001
    ..Here, we have produced a 'molecular map' of the initial vascularization of the developing skeleton that provides a framework in which to interpret a wide range of fetal skeletal malformations, disruptions, and dysplasias...
  64. ncbi Temporospatial expression of tissue inhibitors of matrix metalloproteinases-1, -2 and -3 during development, growth and aging of the mouse skeleton
    K Joronen
    Department of Medical Biochemistry and Molecular Biology, University of Turku, Finland
    Histochem Cell Biol 114:157-65. 2000
    ..These findings suggest that the capacity of articular cartilage chondrocytes to inhibit MMP activities by local production of TIMPs is limited, which may be of consequence during osteoarthritic cartilage degeneration...
  65. ncbi Temporospatial distribution of matrix metalloproteinase and tissue inhibitors of matrix metalloproteinases during murine secondary palate morphogenesis
    J Morris-Wiman
    Department of Orthodontics, College of Dentistry, University of Florida, Gainesville 32610 0444, USA
    Anat Embryol (Berl) 202:129-41. 2000
    ..These results provide support for the idea that temporospatially controlled interactions between MMPs and their substrates may be pivotal in modulating events in palatal morphogenesis...
  66. ncbi Inactivating mutation of the mouse tissue inhibitor of metalloproteinases-2(Timp-2) gene alters proMMP-2 activation
    J J Caterina
    NIDCR Matrix Metalloproteinase Unit and NIDCR Gene Targeting Research and Core Facility, National Institutes of Health, Bethesda, Maryland, 20892 4380, USA
    J Biol Chem 275:26416-22. 2000
    ..e. at low concentrations, TIMP-2 exerts a "catalytic" or enhancing effect on cell-mediated proMMP-2 activation, whereas at higher concentrations, TIMP-2 inhibits the activation and/or activity of MMP-2...
  67. ncbi Matrix metalloproteinases play an active role in Wnt1-induced mammary tumorigenesis
    Laurence Blavier
    Division of Hematology Oncology, Department of Pediatrics, USC Keck School of Medicine, Los Angeles, California, USA
    Cancer Res 66:2691-9. 2006
    ..Thus, for the first time, the data provides evidence for the active role of MMPs in Wnt1-induced mammary tumorigenesis...
  68. ncbi Occurrence and temporal variation in matrix metalloproteinases and their inhibitors during murine secondary palatal morphogenesis
    J Morris-Wiman
    Department of Orthodontics, College of Dentistry, University of Florida, Gainesville, USA
    J Craniofac Genet Dev Biol 19:201-12. 1999
    ..The results of this study demonstrate that MMPs 2, 3, 7, 9 and 13 and TIMPs 1 and 2 and their messages are present during the course of palatal shelf remodelling and that their expression is temporally regulated...
  69. ncbi Matrix metalloproteinases and oral cancer
    G T Thomas
    Department of Oral Pathology, Eastman Dental Institute for Oral Healthcare Sciences, University of London, UK
    Oral Oncol 35:227-33. 1999
    ....
  70. ncbi Alterations of oncogenes, tumor suppressor genes and growth factors in hepatocellular carcinoma: with relation to tumor size and invasiveness
    Z Tang
    Liver Cancer Institute, Shanghai Medical University, China
    Chin Med J (Engl) 111:313-8. 1998
    ..To make a better understanding of the molecular mechanisms involved in recurrence and metastasis of the hepatocellular carcinoma (HCC), some invasion related oncogenes, and growth factors have been investigated...
  71. pmc Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention
    W G Stetler-Stevenson
    Laboratory of Pathology, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20892
    J Clin Invest 103:1237-41. 1999
  72. ncbi Expression of matrix metalloproteinases during murine chorioallantoic placenta maturation
    T Teesalu
    Dipartimento di Ricerca Biologica e Tecnologica DIBIT, Istituto Scientifico S Raffaele, Milano, Italia
    Dev Dyn 214:248-58. 1999
    ..Our findings document the participation of MMPs and their inhibitors in the process of late murine placenta maturation, and warrant the characterization of other members of the MMP family, like membrane type-MMPs, in this process...
  73. ncbi The matrix metalloproteinase-14 (MMP-14) gene is structurally distinct from other MMP genes and is co-expressed with the TIMP-2 gene during mouse embryogenesis
    S S Apte
    Department of Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 272:25511-7. 1997
    ..Mmp14 and the gene for tissue inhibitor of metalloproteinases-2 (Timp2) show a temporally and spatially co-regulated expression during mouse development...
  74. ncbi Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its metanephric developmental regulation with respect to MMP-2 and its inhibitor
    K Ota
    Department of Pathology and Medicine, Northwestern University Medical School, Chicago, Illinois, USA
    Kidney Int 54:131-42. 1998
    ..The activity of MMP-2 is inhibited by a "soluble" tissue inhibitor of MMP-2, TIMP-2. The role of MT-1-MMP in renal development is unknown...
  75. ncbi Matrix metalloproteinases regulate morphogenesis, migration and remodeling of epithelium, tongue skeletal muscle and cartilage in the mandibular arch
    J R Chin
    Department of Anatomy, University of California, San Francisco 94143 0750, USA
    Development 124:1519-30. 1997
    ..Our data suggest that matrix metalloproteinases play a pivotal role in the morphogenesis of structures derived from epithelium (oral sulcus), cranial paraxial mesoderm (tongue) and cranial neural crest (Meckel's cartilage)...
  76. ncbi TIMP-2 promotes cell spreading and adhesion via upregulation of Rap1 signaling
    Hyeujin Chang
    Laboratory of Cellular Oncology, Korea University Graduate School of Medicine, Ansan, Gyeonggi do 425 707, Republic of Korea
    Biochem Biophys Res Commun 345:1201-6. 2006
    ....
  77. 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...
  78. ncbi Differential regulation of TIMP-1, -2, and -3 mRNA and protein expressions during mouse incisor development
    Nagako Yoshiba
    Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences, 5274, Niigata, Japan
    Cell Tissue Res 324:97-104. 2006
    ..Distinct temporal and spatial expression patterns of TIMPs suggest divergent functions of these factors in incisor organogenesis...
  79. pmc Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2 in human microvascular endothelial cells
    Dong Wan Seo
    Cell and Cancer Biology Branch, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892 1500, USA
    J Biol Chem 281:3711-21. 2006
    ....
  80. pmc Tissue inhibitor of metalloproteinase-2(TIMP-2)-deficient mice display motor deficits
    Diane M Jaworski
    Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, 05405, USA
    J Neurobiol 66:82-94. 2006
    ..The tissue specificity of the nerve branching phenotype suggests the involvement of different MMPs and/or extracellular matrix molecules underlying the TIMP-2(-/-) motor phenotype...
  81. pmc The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinases
    Nadia Nour
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    Mol Biol Cell 16:5215-26. 2005
    ..In conclusion, the CRD of PC5A and PACE4 functions as a cell surface anchor favoring the processing of their cognate surface-anchored substrates, including endothelial lipase...
  82. ncbi Differential expression of matrix metalloproteinases and their inhibitors in human and mouse lung development
    Julie Ryu
    University of Giessen Lung Center, Department of Medicine II, Aulweg 123, Room 6 11, D 35392 Giessen, Germany
    Thromb Haemost 94:175-83. 2005
    ..MMP-2, TIMP-2, and TIMP-3 may be key regulatory enzymes during lung development, possibly through their complex action on ECM components, membrane receptor ectodomain shedding, and growth factor bioactivity...
  83. ncbi Murine tissue inhibitor of metalloproteinases-4 (Timp-4): cDNA isolation and expression in adult mouse tissues
    K J Leco
    Department of Medical Biochemistry, University of Calgary, Alberta, Canada
    FEBS Lett 401:213-7. 1997
    ..This pattern of expression distinguishes Timp-4 from other Timps, suggesting that the TIMP-4 protein may be an important tissue-specific regulator of extracellular matrix remodelling...
  84. ncbi Differential expression of tissue inhibitor of metalloproteinases type 1 (TIMP-1) during mouse gonad development
    Romain Guyot
    INSERM U329, Hopital Debrousse, Lyon, France
    Dev Dyn 227:357-66. 2003
    ..Experiments are now under way to determine to what extent TIMP-1 is a morphogenic gene involved in seminiferous cord formation and development...
  85. pmc Lhx2-/- mice develop liver fibrosis
    Ewa Wandzioch
    Umeå Center for Molecular Medicine, Umea University, 901 87 Umea, Sweden
    Proc Natl Acad Sci U S A 101:16549-54. 2004
    ..This study establishes a spontaneous and reproducible animal model for hepatic fibrosis and reveals that Lhx2 expression in HSCs is important for proper cellular organization and differentiation of the liver...
  86. ncbi Expression analysis of the entire MMP and TIMP gene families during mouse tissue development
    Robert K Nuttall
    School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK
    FEBS Lett 563:129-34. 2004
    ....
  87. ncbi Temporospatial gene expression and protein localization of matrix metalloproteinases and their inhibitors during mouse molar tooth development
    Nagako Yoshiba
    Department of Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
    Dev Dyn 228:105-12. 2003
    ..The distinct temporospatial distribution patterns of the TIMPs suggest that these inhibitors play several intrinsic roles during tooth development...
  88. ncbi Structural and functional uncoupling of the enzymatic and angiogenic inhibitory activities of tissue inhibitor of metalloproteinase-2 (TIMP-2): loop 6 is a novel angiogenesis inhibitor
    Cecilia A Fernandez
    Laboratory of Surgical Research, Vascular Biology Program, Children s Hospital Boston, Boston, Massachusetts 02115, USA
    J Biol Chem 278:40989-95. 2003
    ..In addition, we report, for the first time, the discovery of Loop 6 as a novel and potent inhibitor of angiogenesis...
  89. ncbi MT-MMP, the cell surface activator of proMMP-2 (pro-gelatinase A), is expressed with its substrate in mouse tissue during embryogenesis
    H Kinoh
    Departments of Molecular Virology and Oncology, Kanazawa University, Ishikawa, Japan
    J Cell Sci 109:953-9. 1996
    ..These results indicated that proMMP-2 activation through its activator, MT-MMP, is a physiological system used by organisms to initiate tissue remodeling on the cell surface...
  90. ncbi Proteinase expression in early mouse embryos is regulated by leukaemia inhibitory factor and epidermal growth factor
    M B Harvey
    Department of Medical Biochemistry, University of Calgary, Alberta, Canada
    Development 121:1005-14. 1995
    ....
  91. ncbi Matrix metalloproteinases mediate the dismantling of mesenchymal structures in the tadpole tail during thyroid hormone-induced tail resorption
    Jae Chang Jung
    New England Eye Center, Tufts University School of Medicine, 750 Washington Street, Box 450, Boston, MA 02111, USA
    Dev Dyn 223:402-13. 2002
    ..These findings suggest that MMPs and TIMPs act in concert to effect the dismantling of mesenchymal structures during T(3)-induced metamorphic tadpole tail resorption...
  92. pmc Identification of an initiator-like element essential for the expression of the tissue inhibitor of metalloproteinases-4 (Timp-4) gene
    David A Young
    School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, U K
    Biochem J 364:89-99. 2002
    ....
  93. ncbi The expression of tissue inhibitor of metalloproteinase 2 (TIMP-2) is required for normal development of zebrafish embryos
    Jinsong Zhang
    Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA
    Dev Genes Evol 213:382-9. 2003
    ..This is in contrast to murine knockout studies that indicate that TIMP-2 does not have a major role in mouse embryogenesis...
  94. ncbi Expression and function of matrix metalloproteinases and their inhibitors at the maternal-embryonic boundary during mouse embryo implantation
    C M Alexander
    Laboratory of Radiobiology, Department of Biopharmaceutical Sciences, University of California, San Francisco, 94143, USA
    Development 122:1723-36. 1996
    ..We conclude that administration of MMP inhibitors retards decidual remodeling and growth, and we suggest that the MMPs expressed in precursor stromal cells promote their differentiation and expansion...
  95. ncbi Regulation of hepatic fibrosis and extracellular matrix genes by the th response: new insight into the role of tissue inhibitors of matrix metalloproteinases
    B Vaillant
    Schistosomiasis Immunology and Pathology Unit, Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 167:7017-26. 2001
    ..Indeed, our findings suggest that inhibiting profibrotic cytokines or specific MMP may be a more effective strategy to ameliorate fibrotic pathology...
  96. ncbi Substrate choice of membrane-type 1 matrix metalloproteinase is dictated by tissue inhibitor of metalloproteinase-2 levels
    Tomoya Kudo
    Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, 13 1 Takara machi, Kanazawa 920 0934, Japan
    Cancer Sci 98:563-8. 2007
    ..These results suggest that TIMP-2 environment determines MT1-MMP substrate choice between direct cleavage of its own substrates and MMP-2 activation...

Research Grants9

  1. Molecular Regulation of TIMP-2 in Neuron Cell Cycle
    DIANE JAWORSKI; Fiscal Year: 2007
    ..abstract_text> ..
  2. EPITHELIAL/MESENCHYMAL INTERACTIONS IN LUNG DEVELOPMENT
    Farrah Kheradmand; Fiscal Year: 2002
    ..Michael Mafthay, Carol Basbaum, and Gerald Cunha, all senior faculty members of Division of Pulmonary and Department of Anatomy at UCSF. (End of Abstract) ..
  3. Mast Cell Role in Masseter Muscle Repair
    JOYCE MORRIS WIMAN; Fiscal Year: 2005
    ....
  4. The Role of TIMP-1 in Uterine Physiology
    Warren Nothnick; Fiscal Year: 2005
    ..These studies will broaden our understanding on the role of TIMP-1 in uterine physiology and may help to develop new strategies to treat uterine disorders such as infertility, endometriosis and uterine cancer. ..
  5. The Role of Proteinases in Experimental Asthma
    Farrah Kheradmand; Fiscal Year: 2006
    ..Together these findings will substantially contribute to the understanding of regulation of Th2 immunity and will provide new approaches for the treatment of asthma. [unreadable] [unreadable] [unreadable]..
  6. The Role of Proteases in Lung Inflammation & Remodeling
    Farrah Kheradmand; Fiscal Year: 2007
    ..This work may serve as the foundation for future therapeutic studies that target a broad range of asthmatic patients. ..
  7. Estrogen regulation of uterine microRNAs: Novel factors in MMP-9 regulation
    Warren Nothnick; Fiscal Year: 2008
    ..Enhancing our understanding on the regulation of MMP-9 expression may lead to the establishment of novel approaches to counteract mis-expression of this protease and the diseases associated with it. [unreadable] [unreadable] [unreadable]..
  8. Viral-induced T Cell Responses in COPD Exacerbation
    Farrah Kheradmand; Fiscal Year: 2009
    ....
  9. Immune modulators of inflammation in servere COPD
    Farrah Kheradmand; Fiscal Year: 2010
    ..In this application, we will study the role of a subset of cells in the immune system called T helper cells to determine if they could be responsible for the destruction of lung in subjects with COPD and emphysema. ..