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
Products:     Timp2

Top Publications

  1. Pérez Martínez L, Jaworski D. Tissue inhibitor of metalloproteinase-2 promotes neuronal differentiation by acting as an anti-mitogenic signal. J Neurosci. 2005;25:4917-29 pubmed
  2. Fujimoto M, Takagi Y, Aoki T, Hayase M, Marumo T, Gomi M, et al. Tissue inhibitor of metalloproteinases protect blood-brain barrier disruption in focal cerebral ischemia. J Cereb Blood Flow Metab. 2008;28:1674-85 pubmed publisher
    ..These results suggest that TIMP-1 inhibits MMP-9 activity and can play a neuroprotective role in cerebral ischemia. ..
  3. Kandalam V, Basu R, Abraham T, Wang X, Soloway P, Jaworski D, et al. TIMP2 deficiency accelerates adverse post-myocardial infarction remodeling because of enhanced MT1-MMP activity despite lack of MMP2 activation. Circ Res. 2010;106:796-808 pubmed publisher
    ..b>TIMP2 is highly expressed in the heart and is the only TIMP that, in addition to inhibiting MMPs, is required for cell ..
  4. Dang L, Wang Y, Xue Y, He L, Li Y, Xiong J. Low-dose UVB irradiation prevents MMP2-induced skin hyperplasia by inhibiting inflammation and ROS. Oncol Rep. 2015;34:1478-86 pubmed publisher
    ..Further investigation of MMP2 inhibitors of TIMP2/TIMP4 showed an upregulated TIMP2 expression, but not TIMP4...
  5. Chang H, Lee J, Poo H, Noda M, Diaz T, Wei B, et al. TIMP-2 promotes cell spreading and adhesion via upregulation of Rap1 signaling. Biochem Biophys Res Commun. 2006;345:1201-6 pubmed
  6. Nothnick W. Disruption of the tissue inhibitor of metalloproteinase-1 gene results in altered reproductive cyclicity and uterine morphology in reproductive-age female mice. Biol Reprod. 2000;63:905-12 pubmed
    ..It is concluded from this study that TIMP-1 has a multifaceted role in regulating the murine reproductive cycle, and this control appears to be at the level of both the uterus and the ovary. ..
  7. Kisarova Y, Korolenko T. Tissue inhibitors of matrix metalloproteinases 1 and 2 and matrix metalloproteinase activity in the serum and lungs of mice with lewis lung carcinoma. Bull Exp Biol Med. 2012;153:874-7 pubmed
    ..Increased concentration of TIMP-2 in the lungs (but not in the serum) can be regarded as an indicator of Lewis lung carcinoma metastasizing. ..
  8. Nuttall R, Sampieri C, Pennington C, Gill S, Schultz G, Edwards D. Expression analysis of the entire MMP and TIMP gene families during mouse tissue development. FEBS Lett. 2004;563:129-34 pubmed
  9. Kinoh H, Sato H, Tsunezuka Y, Takino T, Kawashima A, Okada Y, et al. MT-MMP, the cell surface activator of proMMP-2 (pro-gelatinase A), is expressed with its substrate in mouse tissue during embryogenesis. J Cell Sci. 1996;109 ( Pt 5):953-9 pubmed
    ..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. ..
  10. Seo D, Li H, Qu C, Oh J, Kim Y, Diaz T, et al. Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2 in human microvascular endothelial cells. J Biol Chem. 2006;281:3711-21 pubmed

Detail Information

Publications86

  1. Pérez Martínez L, Jaworski D. Tissue inhibitor of metalloproteinase-2 promotes neuronal differentiation by acting as an anti-mitogenic signal. J Neurosci. 2005;25:4917-29 pubmed
  2. Fujimoto M, Takagi Y, Aoki T, Hayase M, Marumo T, Gomi M, et al. Tissue inhibitor of metalloproteinases protect blood-brain barrier disruption in focal cerebral ischemia. J Cereb Blood Flow Metab. 2008;28:1674-85 pubmed publisher
    ..These results suggest that TIMP-1 inhibits MMP-9 activity and can play a neuroprotective role in cerebral ischemia. ..
  3. Kandalam V, Basu R, Abraham T, Wang X, Soloway P, Jaworski D, et al. TIMP2 deficiency accelerates adverse post-myocardial infarction remodeling because of enhanced MT1-MMP activity despite lack of MMP2 activation. Circ Res. 2010;106:796-808 pubmed publisher
    ..b>TIMP2 is highly expressed in the heart and is the only TIMP that, in addition to inhibiting MMPs, is required for cell ..
  4. Dang L, Wang Y, Xue Y, He L, Li Y, Xiong J. Low-dose UVB irradiation prevents MMP2-induced skin hyperplasia by inhibiting inflammation and ROS. Oncol Rep. 2015;34:1478-86 pubmed publisher
    ..Further investigation of MMP2 inhibitors of TIMP2/TIMP4 showed an upregulated TIMP2 expression, but not TIMP4...
  5. Chang H, Lee J, Poo H, Noda M, Diaz T, Wei B, et al. TIMP-2 promotes cell spreading and adhesion via upregulation of Rap1 signaling. Biochem Biophys Res Commun. 2006;345:1201-6 pubmed
  6. Nothnick W. Disruption of the tissue inhibitor of metalloproteinase-1 gene results in altered reproductive cyclicity and uterine morphology in reproductive-age female mice. Biol Reprod. 2000;63:905-12 pubmed
    ..It is concluded from this study that TIMP-1 has a multifaceted role in regulating the murine reproductive cycle, and this control appears to be at the level of both the uterus and the ovary. ..
  7. Kisarova Y, Korolenko T. Tissue inhibitors of matrix metalloproteinases 1 and 2 and matrix metalloproteinase activity in the serum and lungs of mice with lewis lung carcinoma. Bull Exp Biol Med. 2012;153:874-7 pubmed
    ..Increased concentration of TIMP-2 in the lungs (but not in the serum) can be regarded as an indicator of Lewis lung carcinoma metastasizing. ..
  8. Nuttall R, Sampieri C, Pennington C, Gill S, Schultz G, Edwards D. Expression analysis of the entire MMP and TIMP gene families during mouse tissue development. FEBS Lett. 2004;563:129-34 pubmed
  9. Kinoh H, Sato H, Tsunezuka Y, Takino T, Kawashima A, Okada Y, et al. MT-MMP, the cell surface activator of proMMP-2 (pro-gelatinase A), is expressed with its substrate in mouse tissue during embryogenesis. J Cell Sci. 1996;109 ( Pt 5):953-9 pubmed
    ..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. ..
  10. Seo D, Li H, Qu C, Oh J, Kim Y, Diaz T, et al. Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2 in human microvascular endothelial cells. J Biol Chem. 2006;281:3711-21 pubmed
  11. Young D, Phillips B, Lundy C, Nuttall R, Hogan A, Schultz G, et al. Identification of an initiator-like element essential for the expression of the tissue inhibitor of metalloproteinases-4 (Timp-4) gene. Biochem J. 2002;364:89-99 pubmed
  12. Caterina J, Yamada S, Caterina N, Longenecker G, Holmbäck K, Shi J, et al. Inactivating mutation of the mouse tissue inhibitor of metalloproteinases-2(Timp-2) gene alters proMMP-2 activation. J Biol Chem. 2000;275:26416-22 pubmed
    ..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. ..
  13. Newby A. Metalloproteinases promote plaque rupture and myocardial infarction: A persuasive concept waiting for clinical translation. Matrix Biol. 2015;44-46:157-66 pubmed publisher
    ..Overcoming these barriers would open the way to new treatments that could have a major impact on cardiovascular mortality worldwide. ..
  14. Blavier L, Lazaryev A, Groffen J, Heisterkamp N, DeClerck Y, Kaartinen V. TGF-beta3-induced palatogenesis requires matrix metalloproteinases. Mol Biol Cell. 2001;12:1457-66 pubmed
    ..Our observations indicate for the first time that the proteolytic degradation of the ECM by MMPs is a necessary step for palatal fusion. ..
  15. Li F, Ma N, Zhao R, Wu G, Zhang Y, Qiao Y, et al. Overexpression of miR-483-5p/3p cooperate to inhibit mouse liver fibrosis by suppressing the TGF-? stimulated HSCs in transgenic mice. J Cell Mol Med. 2014;18:966-74 pubmed publisher
    ..Our work identifies the pathway that regulates liver fibrosis by inhibiting the activation of HSCs. ..
  16. Sahlberg C, Reponen P, Tryggvason K, Thesleff I. Timp-1, -2 and -3 show coexpression with gelatinases A and B during mouse tooth morphogenesis. Eur J Oral Sci. 1999;107:121-30 pubmed
  17. Yoshiba N, Yoshiba K, Stoetzel C, Perrin Schmitt F, Cam Y, Ruch J, et al. Differential regulation of TIMP-1, -2, and -3 mRNA and protein expressions during mouse incisor development. Cell Tissue Res. 2006;324:97-104 pubmed
    ..Distinct temporal and spatial expression patterns of TIMPs suggest divergent functions of these factors in incisor organogenesis. ..
  18. Colnot C, Helms J. A molecular analysis of matrix remodeling and angiogenesis during long bone development. Mech Dev. 2001;100:245-50 pubmed
    ..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. ..
  19. Rankin C, Suzuki K, Itoh Y, Ziemer D, Grantham J, Calvet J, et al. Matrix metalloproteinases and TIMPS in cultured C57BL/6J-cpk kidney tubules. Kidney Int. 1996;50:835-44 pubmed
    ..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. ..
  20. Thomas G, Lewis M, Speight P. Matrix metalloproteinases and oral cancer. Oral Oncol. 1999;35:227-33 pubmed
  21. Morris Wiman J, Du Y, Brinkley L. Occurrence and temporal variation in matrix metalloproteinases and their inhibitors during murine secondary palatal morphogenesis. J Craniofac Genet Dev Biol. 1999;19:201-12 pubmed
    ..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. ..
  22. Shimoda M, Principe S, Jackson H, Luga V, Fang H, Molyneux S, et al. Loss of the Timp gene family is sufficient for the acquisition of the CAF-like cell state. Nat Cell Biol. 2014;16:889-901 pubmed publisher
    ..Thus, Timps suppress cancer stroma where activated-fibroblast-secreted exosomes impact tumour progression...
  23. Kim K, Burkhart K, Chen P, Frevert C, Randolph Habecker J, Hackman R, et al. Tissue inhibitor of metalloproteinase-1 deficiency amplifies acute lung injury in bleomycin-exposed mice. Am J Respir Cell Mol Biol. 2005;33:271-9 pubmed
    ..Our results provide direct evidence that TIMP-1 contributes significantly to the regulation of acute lung injury, functioning to limit inflammation and lung permeability. ..
  24. Blavier L, Lazaryev A, Dorey F, Shackleford G, DeClerck Y. Matrix metalloproteinases play an active role in Wnt1-induced mammary tumorigenesis. Cancer Res. 2006;66:2691-9 pubmed
    ..Thus, for the first time, the data provides evidence for the active role of MMPs in Wnt1-induced mammary tumorigenesis. ..
  25. Das S, Yano S, Wang J, Edwards D, Nagase H, Dey S. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in the mouse uterus during the peri-implantation period. Dev Genet. 1997;21:44-54 pubmed
  26. Stetler Stevenson W. Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J Clin Invest. 1999;103:1237-41 pubmed
  27. Lei Y, Yang J, Zhao H. [Experimental study on extracts from ginseng, notoginseng and chuanxiong for delaying vascular aging in senescent mice]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2010;30:946-51 pubmed
  28. Kim B, Abdel Rahman M, Wang T, Pouly S, Mahmoud A, Cebulla C. Retinal MMP-12, MMP-13, TIMP-1, and TIMP-2 expression in murine experimental retinal detachment. Invest Ophthalmol Vis Sci. 2014;55:2031-40 pubmed publisher
    ..Immunohistochemistry revealed moderate to strong MMP-13 levels in subretinal space macrophages. Fibrosis can develop in the HA-RD model. There is an upregulation of select MMPs that may modulate the wound healing process following RD. ..
  29. Sabeh F, Li X, Saunders T, Rowe R, Weiss S. Secreted versus membrane-anchored collagenases: relative roles in fibroblast-dependent collagenolysis and invasion. J Biol Chem. 2009;284:23001-11 pubmed publisher
    ..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. ..
  30. Jung J, Leco K, Edwards D, Fini M. Matrix metalloproteinases mediate the dismantling of mesenchymal structures in the tadpole tail during thyroid hormone-induced tail resorption. Dev Dyn. 2002;223:402-13 pubmed
    ..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. ..
  31. Mattot V, Raes M, Henriet P, Eeckhout Y, Stehelin D, Vandenbunder B, et al. Expression of interstitial collagenase is restricted to skeletal tissue during mouse embryogenesis. J Cell Sci. 1995;108 ( Pt 2):529-35 pubmed
  32. Smith L, Wagner T, Huizar I, Schnapp L. uPARAP expression during murine lung development. Gene Expr Patterns. 2008;8:486-93 pubmed publisher
    ..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. ..
  33. Lluri G, Langlois G, McClellan B, Soloway P, Jaworski D. Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates neuromuscular junction development via a beta1 integrin-mediated mechanism. J Neurobiol. 2006;66:1365-77 pubmed
    ..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. ..
  34. Sinno M, Biagioni S, Ajmone Cat M, Pafumi I, Caramanica P, Medda V, et al. The matrix metalloproteinase inhibitor marimastat promotes neural progenitor cell differentiation into neurons by gelatinase-independent TIMP-2-dependent mechanisms. Stem Cells Dev. 2013;22:345-58 pubmed publisher
  35. Nour N, Mayer G, Mort J, Salvas A, Mbikay M, Morrison C, et al. 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. Mol Biol Cell. 2005;16:5215-26 pubmed
    ..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. ..
  36. Shimizu S, Malik K, Sejima H, Kishi J, Hayakawa T, Koiwai O. Cloning and sequencing of the cDNA encoding a mouse tissue inhibitor of metalloproteinase-2. Gene. 1992;114:291-2 pubmed
    ..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. ..
  37. Vaillant B, Chiaramonte M, Cheever A, Soloway P, Wynn T. Regulation of hepatic fibrosis and extracellular matrix genes by the th response: new insight into the role of tissue inhibitors of matrix metalloproteinases. J Immunol. 2001;167:7017-26 pubmed
    ..Indeed, our findings suggest that inhibiting profibrotic cytokines or specific MMP may be a more effective strategy to ameliorate fibrotic pathology. ..
  38. Wandzioch E, Kolterud A, Jacobsson M, Friedman S, Carlsson L. Lhx2-/- mice develop liver fibrosis. Proc Natl Acad Sci U S A. 2004;101:16549-54 pubmed
    ..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. ..
  39. Lluri G, Langlois G, Soloway P, Jaworski D. Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates myogenesis and beta1 integrin expression in vitro. Exp Cell Res. 2008;314:11-24 pubmed
    ..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. ..
  40. Kishi J, Ogawa K, Yamamoto S, Hayakawa T. Purification and characterization of a new tissue inhibitor of metalloproteinases (TIMP-2) from mouse colon 26 tumor cells. Matrix. 1991;11:10-6 pubmed
    ..NH2-Terminal protein sequence data were obtained for the first 36 residues of the colon 26 inhibitor, and the first 20 of them exhibited a sequence almost identical with that of a new TIMP recently designated as TIMP-2. ..
  41. Kudo T, Takino T, Miyamori H, Thompson E, Sato H. Substrate choice of membrane-type 1 matrix metalloproteinase is dictated by tissue inhibitor of metalloproteinase-2 levels. Cancer Sci. 2007;98:563-8 pubmed
    ..These results suggest that TIMP-2 environment determines MT1-MMP substrate choice between direct cleavage of its own substrates and MMP-2 activation. ..
  42. Leco K, Hayden L, Sharma R, Rocheleau H, Greenberg A, Edwards D. Differential regulation of TIMP-1 and TIMP-2 mRNA expression in normal and Ha-ras-transformed murine fibroblasts. Gene. 1992;117:209-17 pubmed
    ..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. ..
  43. English J, Kassiri Z, Koskivirta I, Atkinson S, Di Grappa M, Soloway P, et al. Individual Timp deficiencies differentially impact pro-MMP-2 activation. J Biol Chem. 2006;281:10337-46 pubmed
    ..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. ..
  44. Lee D, Watson M, Seldin M. Mouse Cd7 maps to chromosome 11. Immunogenetics. 1994;39:289-90 pubmed
  45. Xu J, Wang P, Wang T, Wang M, Chen S, Yu P, et al. Effects of reduced ?2-glycoprotein I on the expression of aortic matrix metalloproteinases and tissue inhibitor matrix metalloproteinases in diabetic mice. BMC Cardiovasc Disord. 2014;14:114 pubmed publisher
    ..In the aortas, reduced ?(2)GP I decreased MMP2/TIMP2 mRNA and protein expression levels, and MMP9/TIMP1 expression levels compared with those in diabetic controls...
  46. Blavier L, DeClerck Y. Tissue inhibitor of metalloproteinases-2 is expressed in the interstitial matrix in adult mouse organs and during embryonic development. Mol Biol Cell. 1997;8:1513-27 pubmed
    ..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. ..
  47. Nishino K, Yamanouchi K, Naito K, Tojo H. Matrix metalloproteinases regulate mesonephric cell migration in developing XY gonads which correlates with the inhibition of tissue inhibitor of metalloproteinase-3 by Sry. Dev Growth Differ. 2002;44:35-43 pubmed
    ..These findings are an important clue for the elucidation of testicular formation in developing gonads. ..
  48. Fernandez C, Butterfield C, Jackson G, Moses M. 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. J Biol Chem. 2003;278:40989-95 pubmed
    ..In addition, we report, for the first time, the discovery of Loop 6 as a novel and potent inhibitor of angiogenesis. ..
  49. Tang Z, Qin L, Wang X, Zhou G, Liao Y, Weng Y, et al. Alterations of oncogenes, tumor suppressor genes and growth factors in hepatocellular carcinoma: with relation to tumor size and invasiveness. Chin Med J (Engl). 1998;111:313-8 pubmed
    ..Expression of nm23/TIMP-2 was closely related to the prognosis of HCC patients. Biological characteristics remained critical points to the prognosis even in small HCC. ..
  50. Wu Z, Horgan C, Carr O, Owens R, Iozzo R, Lechner B. Biglycan and decorin differentially regulate signaling in the fetal membranes. Matrix Biol. 2014;35:266-75 pubmed publisher
  51. Gomes J, Omar N, Dos Santos Neves J, Narvaes E, Novaes P. Increase of MT1-MMP, TIMP-2 and Ki-67 proteins in the odontogenic region of the rat incisor post-shortening procedure. J Mol Histol. 2010;41:333-41 pubmed publisher
    ..This suggests that MT1-MMP and TIMP-2 may have some role in cell proliferation during the eruption of the rat incisor tooth. ..
  52. De Clerck Y, Szpirer C, Aly M, Cassiman J, Eeckhout Y, Rousseau G. The gene for tissue inhibitor of metalloproteinases-2 is localized on human chromosome arm 17q25. Genomics. 1992;14:782-4 pubmed
    Tissue inhibitor of metalloproteinases-2 (TIMP2) is a natural inhibitor of several proteinases that are involved in the degradation of the extracellular matrix...
  53. Guan Y, Ackert Bicknell C, Kell B, Troyanskaya O, Hibbs M. Functional genomics complements quantitative genetics in identifying disease-gene associations. PLoS Comput Biol. 2010;6:e1000991 pubmed publisher
    ..predictions (not observed in any previous GWAS/QTL studies) and found significant bone density defects for both Timp2 and Abcg8 deficient mice...
  54. Ryu J, Vicencio A, Yeager M, Kashgarian M, Haddad G, Eickelberg O. Differential expression of matrix metalloproteinases and their inhibitors in human and mouse lung development. Thromb Haemost. 2005;94:175-83 pubmed
    ..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. ..
  55. Yoshiba N, Yoshiba K, Stoetzel C, Perrin Schmitt F, Cam Y, Ruch J, et al. Temporospatial gene expression and protein localization of matrix metalloproteinases and their inhibitors during mouse molar tooth development. Dev Dyn. 2003;228:105-12 pubmed
    ..The distinct temporospatial distribution patterns of the TIMPs suggest that these inhibitors play several intrinsic roles during tooth development. ..
  56. Woods C, Sundar K, Tessler C, Lebsack T, Grainger L, Nielsen A, et al. Tissue inhibitor of metalloproteinase-2 inhibits T-cell infiltration and preserves pancreatic beta-cell function in an in vitro type 1 diabetes mellitus model. J Autoimmun. 2006;27:28-37 pubmed
    ..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. ..
  57. Reponen P, Leivo I, Sahlberg C, Apte S, Olsen B, Thesleff I, et al. 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. Dev Dyn. 1995;202:388-96 pubmed
    ..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. ..
  58. Morrison C, Overall C. TIMP independence of matrix metalloproteinase (MMP)-2 activation by membrane type 2 (MT2)-MMP is determined by contributions of both the MT2-MMP catalytic and hemopexin C domains. J Biol Chem. 2006;281:26528-39 pubmed
    ..This contribution may be mediated in part through MMP-2 activation by MT2-MMP. Using Timp2-/- cells, we previously demonstrated that MT2-MMP activates MMP-2 to the fully active form in a pathway that is ..
  59. Yao P, Lin Y, Richburg J. Transcriptional suppression of Sertoli cell Timp2 in rodents following mono-(2-ethylhexyl) phthalate exposure is regulated by CEBPA and MYC. Biol Reprod. 2011;85:1203-15 pubmed publisher
    ..prototypical testicular toxic phthalate monoester, mono-(2-ethylhexyl) phthalate (MEHP), suppresses Sertoli cell TIMP2 levels and allows for the activation of MMP2 in seminiferous epithelium...
  60. Gompers A, Su Feher L, Ellegood J, Copping N, Riyadh M, Stradleigh T, et al. Germline Chd8 haploinsufficiency alters brain development in mouse. Nat Neurosci. 2017;20:1062-1073 pubmed publisher
    ..This integrative analysis offers an initial picture of the consequences of Chd8 haploinsufficiency for brain development. ..
  61. Di Gregoli K, George S, Jackson C, Newby A, Johnson J. Differential effects of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 on atherosclerosis and monocyte/macrophage invasion. Cardiovasc Res. 2016;109:318-30 pubmed publisher
    ..Our data demonstrate that TIMP-2 plays a greater protective role than TIMP-1 during the pathogenesis of atherosclerosis, in part by suppressing MMP-14-dependent monocyte/macrophage accumulation into plaques. ..
  62. Morris Wiman J, Burch H, Basco E. Temporospatial distribution of matrix metalloproteinase and tissue inhibitors of matrix metalloproteinases during murine secondary palate morphogenesis. Anat Embryol (Berl). 2000;202:129-41 pubmed
    ..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. ..
  63. Fujimoto N, Tokai H, Iwata K, Okada Y, Hayakawa T. Determination of tissue inhibitor of metalloproteinases-2 (TIMP-2) in experimental animals using monoclonal antibodies against TIMP-2-specific oligopeptides. J Immunol Methods. 1995;187:33-9 pubmed
    ..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. ..
  64. Basu R, Lee J, Morton J, Takawale A, Fan D, Kandalam V, et al. TIMP3 is the primary TIMP to regulate agonist-induced vascular remodelling and hypertension. Cardiovasc Res. 2013;98:360-71 pubmed publisher
    ..TIMP-knockout mice to angiotensin II (Ang II) infusion, and found that Ang-II-induced hypertension in TIMP1(-/-), TIMP2(-/-), and TIMP4(-/-) mice was comparable to wild-type (WT) mice, but significantly suppressed in TIMP3(-/-) mice...
  65. Lima A, Francelin C, Ferrucci D, Stach Machado D, Verinaud L. Thymic alterations induced by Plasmodium berghei: expression of matrix metalloproteinases and their tissue inhibitors. Cell Immunol. 2012;279:53-9 pubmed publisher
    ..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. ..
  66. FOSTER C, Daniel L, Daniels C, Dalal S, Singh M, Singh K. Deficiency of ataxia telangiectasia mutated kinase modulates cardiac remodeling following myocardial infarction: involvement in fibrosis and apoptosis. PLoS ONE. 2013;8:e83513 pubmed publisher
    ..In vitro, inhibition of ATM using KU-55933 increased oxidative stress and apoptosis in cardiac myocytes. ..
  67. Hans C, Feng Y, Naura A, Troxclair D, Zerfaoui M, Siddiqui D, et al. Opposing roles of PARP-1 in MMP-9 and TIMP-2 expression and mast cell degranulation in dyslipidemic dilated cardiomyopathy. Cardiovasc Pathol. 2011;20:e57-68 pubmed publisher
    ..With additional protective effects against cell death and inflammation, PARP-1 deficiency preserves cardiac tissue homeostasis. ..
  68. Mi M, Shi S, Li T, Holz J, Lee Y, Sheu T, et al. TIMP2 deficient mice develop accelerated osteoarthritis via promotion of angiogenesis upon destabilization of the medial meniscus. Biochem Biophys Res Commun. 2012;423:366-72 pubmed publisher
    ..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 ..
  69. Apte S, Fukai N, Beier D, Olsen B. 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. J Biol Chem. 1997;272:25511-7 pubmed
    ..Mmp14 and the gene for tissue inhibitor of metalloproteinases-2 (Timp2) show a temporally and spatially co-regulated expression during mouse development...
  70. Greene A, Puder M, Roy R, Kilroy S, Louis G, Folkman J, et al. Urinary matrix metalloproteinases and their endogenous inhibitors predict hepatic regeneration after murine partial hepatectomy. Transplantation. 2004;78:1139-44 pubmed
  71. Bednarek N, Clément Y, Lelievre V, Olivier P, Loron G, Garnotel R, et al. Ontogeny of MMPs and TIMPs in the murine neocortex. Pediatr Res. 2009;65:296-300 pubmed publisher
    ..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. ..
  72. Alexander C, Hansell E, Behrendtsen O, Flannery M, Kishnani N, Hawkes S, et al. Expression and function of matrix metalloproteinases and their inhibitors at the maternal-embryonic boundary during mouse embryo implantation. Development. 1996;122:1723-36 pubmed
    ..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. ..
  73. Castellano J, Mosher K, Abbey R, McBride A, James M, Berdnik D, et al. Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature. 2017;544:488-492 pubmed publisher
    ..b>Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor enriched in human cord plasma, young mouse plasma, and young mouse ..
  74. Tveita A, Rekvig O, Zykova S. Increased glomerular matrix metalloproteinase activity in murine lupus nephritis. Kidney Int. 2008;74:1150-8 pubmed publisher
    ..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. ..
  75. Stratman A, Saunders W, Sacharidou A, Koh W, Fisher K, Zawieja D, et al. Endothelial cell lumen and vascular guidance tunnel formation requires MT1-MMP-dependent proteolysis in 3-dimensional collagen matrices. Blood. 2009;114:237-47 pubmed publisher
    ..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. ..
  76. Ota K, Stetler Stevenson W, Yang Q, Kumar A, Wada J, Kashihara N, et al. Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its metanephric developmental regulation with respect to MMP-2 and its inhibitor. Kidney Int. 1998;54:131-42 pubmed
  77. Legallicier B, Trugnan G, Murphy G, Lelongt B, Ronco P. Expression of the type IV collagenase system during mouse kidney development and tubule segmentation. J Am Soc Nephrol. 2001;12:2358-69 pubmed
    ..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 ..
  78. Kheradmand F, Rishi K, Werb Z. Signaling through the EGF receptor controls lung morphogenesis in part by regulating MT1-MMP-mediated activation of gelatinase A/MMP2. J Cell Sci. 2002;115:839-48 pubmed
    ..MT1-MMP is, in turn, necessary for activation of MMP-2, a mesenchymal enzyme that is required for normal lung morphogenesis. ..
  79. Li S, Guo J, Wu J, Sun Z, Han M, Shan S, et al. miR-17 targets tissue inhibitor of metalloproteinase 1 and 2 to modulate cardiac matrix remodeling. FASEB J. 2013;27:4254-65 pubmed publisher
    ..Chimeric luciferase reporter constructs were cloned for miR-17 target validation. miR-17 targeted the 3'-UTR of TIMP2 and the protein coding region of TIMP1. The miR-17 mimic decreased TIMP2 (P<0.01) and TIMP1 (P<0...
  80. Jaworski D, Soloway P, Caterina J, Falls W. Tissue inhibitor of metalloproteinase-2(TIMP-2)-deficient mice display motor deficits. J Neurobiol. 2006;66:82-94 pubmed
    ..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. Yoshiba N, Yoshiba K, Hosoya A, Saito M, Yokoi T, Okiji T, et al. Association of TIMP-2 with extracellular matrix exposed to mechanical stress and its co-distribution with periostin during mouse mandible development. Cell Tissue Res. 2007;330:133-45 pubmed
    ..We suggest that TIMP-2 and periostin are co-distributed on ECM exposed to mechanical forces and coordinately function as ECM modulators. ..
  82. Aoki T, Kataoka H, Moriwaki T, Nozaki K, Hashimoto N. Role of TIMP-1 and TIMP-2 in the progression of cerebral aneurysms. Stroke. 2007;38:2337-45 pubmed
    ..There is an imbalance between MMPs and TIMPs in the late stage of cerebral aneurysm formation, which may be responsible for ECM degradation leading to the progression and rupture of cerebral aneurysms. ..
  83. Jackson H, Hojilla C, Weiss A, Sanchez O, Wood G, Khokha R. Timp3 deficient mice show resistance to developing breast cancer. PLoS ONE. 2015;10:e0120107 pubmed publisher
    ..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. ..
  84. Zhang J, Bai S, Tanase C, Nagase H, Sarras M. The expression of tissue inhibitor of metalloproteinase 2 (TIMP-2) is required for normal development of zebrafish embryos. Dev Genes Evol. 2003;213:382-9 pubmed
    ..This is in contrast to murine knockout studies that indicate that TIMP-2 does not have a major role in mouse embryogenesis. ..