Gene Symbol: Timp3
Description: tissue inhibitor of metalloproteinase 3
Alias: Timp-3, metalloproteinase inhibitor 3, tissue inhibitor of metalloproteinases 3
Species: mouse
Products:     Timp3

Top Publications

  1. 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. ..
  2. Schorpp Kistner M, Wang Z, Angel P, Wagner E. JunB is essential for mammalian placentation. EMBO J. 1999;18:934-48 pubmed
    ..Therefore, JunB appears to be involved in multiple signaling pathways regulating genes involved in the establishment of a proper feto-maternal circulatory system. ..
  3. Tanaka F, Sonoda H, Okamoto M, Mimori K, Utsunomiya T, Inoue H, et al. TIMP-3 and Phosphatidylinositol 3-kinase genes were found to be related to the progression of colon cancer in a comparison of pneumoperitoneum and laparotomy in a murine model. Surg Today. 2007;37:220-5 pubmed
  4. Wetzel M, Li L, Harms K, Roitbak T, Ventura P, Rosenberg G, et al. Tissue inhibitor of metalloproteinases-3 facilitates Fas-mediated neuronal cell death following mild ischemia. Cell Death Differ. 2008;15:143-51 pubmed
    ..These studies demonstrate that TIMP-3 facilitates Fas-mediated neuronal cell death following OGD and plays a pro-apoptotic role in mild cerebral ischemia. ..
  5. Murthy A, Defamie V, Smookler D, Di Grappa M, Horiuchi K, Federici M, et al. Ectodomain shedding of EGFR ligands and TNFR1 dictates hepatocyte apoptosis during fulminant hepatitis in mice. J Clin Invest. 2010;120:2731-44 pubmed publisher
    ..b>Tissue inhibitor of metalloproteinases 3 (TIMP3) controls the critical sheddase a disintegrin and metalloproteinase 17 (ADAM17) and may ..
  6. Kassiri Z, Defamie V, Hariri M, Oudit G, Anthwal S, Dawood F, et al. Simultaneous transforming growth factor beta-tumor necrosis factor activation and cross-talk cause aberrant remodeling response and myocardial fibrosis in Timp3-deficient heart. J Biol Chem. 2009;284:29893-904 pubmed publisher
    ..We reported that the loss of Timp3 (tissue inhibitor of metalloproteinase 3) leads to abnormal TNF signaling and cardiovascular function...
  7. Kassiri Z, Oudit G, Sanchez O, Dawood F, Mohammed F, Nuttall R, et al. Combination of tumor necrosis factor-alpha ablation and matrix metalloproteinase inhibition prevents heart failure after pressure overload in tissue inhibitor of metalloproteinase-3 knock-out mice. Circ Res. 2005;97:380-90 pubmed
    ..Notably, combining TNFalpha ablation with MMP inhibition completely rescued heart disease in timp-3(-/-)-AB mice. This study provides a basis for anti-TNFalpha and MMP inhibitor combination therapy in heart disease. ..
  8. Spurbeck W, Ng C, Strom T, Vanin E, Davidoff A. Enforced expression of tissue inhibitor of matrix metalloproteinase-3 affects functional capillary morphogenesis and inhibits tumor growth in a murine tumor model. Blood. 2002;100:3361-8 pubmed
  9. Qi J, Ebrahem Q, Moore N, Murphy G, Claesson Welsh L, Bond M, et al. A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med. 2003;9:407-15 pubmed
    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)...

More Information


  1. Smookler D, Mohammed F, Kassiri Z, Duncan G, Mak T, Khokha R. Tissue inhibitor of metalloproteinase 3 regulates TNF-dependent systemic inflammation. J Immunol. 2006;176:721-5 pubmed
    ..by TNF-alpha converting enzyme, which is selectively inhibited by the tissue inhibitor of metalloproteinase 3 (TIMP3). We show that loss of TIMP3 impacts innate immunity by dysregulating cleavage of TNF and its receptors...
  2. Kawamoto H, Yasuda O, Suzuki T, Ozaki T, Yotsui T, Higuchi M, et al. Tissue inhibitor of metalloproteinase-3 plays important roles in the kidney following unilateral ureteral obstruction. Hypertens Res. 2006;29:285-94 pubmed
    ..These findings indicate that Timp-3-deficiency does not substantially affect the blood pressure in mice, and that Timp-3 plays an important role in the maintenance of renal macrostructure after unilateral ureteral obstruction. ..
  3. Saunders W, Bohnsack B, Faske J, Anthis N, Bayless K, Hirschi K, et al. Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3. J Cell Biol. 2006;175:179-91 pubmed
  4. Fiorentino L, Vivanti A, Cavalera M, Marzano V, Ronci M, Fabrizi M, et al. Increased tumor necrosis factor alpha-converting enzyme activity induces insulin resistance and hepatosteatosis in mice. Hepatology. 2010;51:103-10 pubmed publisher
    ..To test the role of TACE activation in vivo, we used tissue inhibitor of metalloproteinase 3 (Timp3) null mice, because Timp3 is the specific inhibitor of TACE and Timp3(-/-) mice have higher TACE activity compared ..
  5. Bernot D, Barruet E, Poggi M, Bonardo B, Alessi M, Peiretti F. Down-regulation of tissue inhibitor of metalloproteinase-3 (TIMP-3) expression is necessary for adipocyte differentiation. J Biol Chem. 2010;285:6508-14 pubmed publisher
    ..Our results indicate that during preadipocyte differentiation, the Sp1-dependent decrease in TIMP-3 expression is required for the successful implementation of the adipocyte differentiation program. ..
  6. Tian H, Cimini M, Fedak P, Altamentova S, Fazel S, Huang M, et al. TIMP-3 deficiency accelerates cardiac remodeling after myocardial infarction. J Mol Cell Cardiol. 2007;43:733-43 pubmed
    ..This study supports further investigations to determine whether such remodeling could be reduced by augmenting TIMP-3 expression in the infarcted myocardium. ..
  7. Kassiri Z, Oudit G, Kandalam V, Awad A, Wang X, Ziou X, et al. Loss of TIMP3 enhances interstitial nephritis and fibrosis. J Am Soc Nephrol. 2009;20:1223-35 pubmed publisher
    ..b>TIMP3 is the most highly expressed tissue inhibitor of metalloproteinase (TIMP) in the kidney, but its function in renal ..
  8. Federici M, Hribal M, Menghini R, Kanno H, Marchetti V, Porzio O, et al. Timp3 deficiency in insulin receptor-haploinsufficient mice promotes diabetes and vascular inflammation via increased TNF-alpha. J Clin Invest. 2005;115:3494-505 pubmed
    ..receptor heterozygous (Insr+/-) mice, we identified the deficiency of tissue inhibitor of metalloproteinase 3 (Timp3, an inhibitor of both TNF-alpha-converting enzyme [TACE] and MMPs) as a common bond between glucose intolerance ..
  9. Apte S, Olsen B, Murphy G. The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP gene family. J Biol Chem. 1995;270:14313-8 pubmed
    ..F., Mattei, M-G., Hayashi, M., and Olsen, B. R. (1994) Dev. Dynam. 200, 177-197); the identification of TIMP3 mutations in Sorsby's fundus dystrophy has underscored the functional importance of TIMP-3...
  10. Mohammed F, Smookler D, Taylor S, Fingleton B, Kassiri Z, Sanchez O, et al. Abnormal TNF activity in Timp3-/- mice leads to chronic hepatic inflammation and failure of liver regeneration. Nat Genet. 2004;36:969-77 pubmed
    ..Here we show that deletion of the mouse gene Timp3 resulted in an increase in TNF-alpha converting enzyme activity, constitutive release of TNF and activation of TNF ..
  11. Menghini R, Menini S, Amoruso R, Fiorentino L, Casagrande V, Marzano V, et al. Tissue inhibitor of metalloproteinase 3 deficiency causes hepatic steatosis and adipose tissue inflammation in mice. Gastroenterology. 2009;136:663-72.e4 pubmed publisher
    ..Decreased expression of tissue inhibitor of metalloproteinase 3 (Timp3) is a catalyst for insulin resistance and inflammation...
  12. Liu H, Chen S, Jin B, Carson J, Niu A, Durham W, et al. TIMP3: a physiological regulator of adult myogenesis. J Cell Sci. 2010;123:2914-21 pubmed publisher
    ..In the present study, we demonstrate that tissue inhibitor of metalloproteinase 3 (TIMP3), the endogenous inhibitor of TNFalpha-converting enzyme (TACE), acts as an on-off switch for myogenic ..
  13. 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
    ..TIMP1(-/-), TIMP2(-/-), and TIMP4(-/-) mice was comparable to wild-type (WT) mice, but significantly suppressed in TIMP3(-/-) mice...
  14. Fata J, Leco K, Voura E, Yu H, Waterhouse P, Murphy G, et al. Accelerated apoptosis in the Timp-3-deficient mammary gland. J Clin Invest. 2001;108:831-41 pubmed
    ..The physiological relevance of TIMP-3 became apparent as Timp-3(-/-) dams failed to reestablish lactation after brief cessation of suckling. Thus, TIMP-3 is a critical epithelial survival factor during mammary gland involution. ..
  15. Janssen A, Hoellenriegel J, Fogarasi M, Schrewe H, Seeliger M, Tamm E, et al. Abnormal vessel formation in the choroid of mice lacking tissue inhibitor of metalloprotease-3. Invest Ophthalmol Vis Sci. 2008;49:2812-22 pubmed publisher
    ..In the eye, TIMP3 is tightly associated with Bruch's membrane...
  16. Murthy A, Shao Y, Defamie V, Wedeles C, Smookler D, Khokha R. Stromal TIMP3 regulates liver lymphocyte populations and provides protection against Th1 T cell-driven autoimmune hepatitis. J Immunol. 2012;188:2876-83 pubmed publisher
    ..b>Tissue inhibitor of metalloproteinases 3 (TIMP3) controls systemic cytokine bioavailability and signaling by inhibiting the ectodomain ..
  17. Mahmoodi M, Sahebjam S, Smookler D, Khokha R, Mort J. Lack of tissue inhibitor of metalloproteinases-3 results in an enhanced inflammatory response in antigen-induced arthritis. Am J Pathol. 2005;166:1733-40 pubmed
    ..To determine the relative importance of this inhibitor in joint pathology, wild-type and Timp3-/- mice were immunized with methylated bovine serum albumin followed by arthritis induction by intra-articular ..
  18. Nagahama Y, Sone M, Chen X, Okada Y, Yamamoto M, Xin B, et al. Contributions of hepatocytes and bile ductular cells in ductular reactions and remodeling of the biliary system after chronic liver injury. Am J Pathol. 2014;184:3001-12 pubmed publisher
    ..We conclude that hepatocytes and bile ducts or ductules are important sources of ductular reaction and that the intrahepatic biliary system undergoes remarkable remodeling in response to chronic liver injury. ..
  19. Hewing N, Weskamp G, Vermaat J, Farage E, Glomski K, Swendeman S, et al. Intravitreal injection of TIMP3 or the EGFR inhibitor erlotinib offers protection from oxygen-induced retinopathy in mice. Invest Ophthalmol Vis Sci. 2013;54:864-70 pubmed publisher
    ..we tested how genetic inactivation of a physiological ADAM17 inhibitor, the tissue inhibitor of matrix metalloproteinases-3 (TIMP3), or intravitreal injection of TIMP3 or of the EGFR inhibitor erlotinib influenced the outcome of OIR.
  20. Le Gall S, Maretzky T, Issuree P, Niu X, Reiss K, Saftig P, et al. ADAM17 is regulated by a rapid and reversible mechanism that controls access to its catalytic site. J Cell Sci. 2010;123:3913-22 pubmed publisher
    ..on removal of its inhibitory pro-domain by pro-protein convertases, or on dissociation of an endogenous inhibitor, TIMP3. Moreover, activation of ADAM17 by physiological stimuli requires its transmembrane domain, but not its ..
  21. 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. ..
  22. Kandalam V, Basu R, Abraham T, Wang X, Awad A, Wang W, et al. Early activation of matrix metalloproteinases underlies the exacerbated systolic and diastolic dysfunction in mice lacking TIMP3 following myocardial infarction. Am J Physiol Heart Circ Physiol. 2010;299:H1012-23 pubmed publisher
    ..b>TIMP3 is highly expressed in the heart, and is markedly downregulated in patients with ischemic cardiomyopathy...
  23. Stetler Stevenson W. Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J Clin Invest. 1999;103:1237-41 pubmed
  24. Rancourt S, Rancourt D. Murine subtilisin-like proteinase SPC6 is expressed during embryonic implantation, somitogenesis, and skeletal formation. Dev Genet. 1997;21:75-81 pubmed
  25. Apte S, Hayashi K, Seldin M, Mattei M, Hayashi M, Olsen B. Gene encoding a novel murine tissue inhibitor of metalloproteinases (TIMP), TIMP-3, is expressed in developing mouse epithelia, cartilage, and muscle, and is located on mouse chromosome 10. Dev Dyn. 1994;200:177-97 pubmed
    ..We propose a role for TIMP-3 in musculoskeletal and cardiac development, in the morphogenesis of certain epithelial structures, and placental implantation. ..
  26. Mandal M, Vasireddy V, Reddy G, Wang X, Moroi S, Pattnaik B, et al. CTRP5 is a membrane-associated and secretory protein in the RPE and ciliary body and the S163R mutation of CTRP5 impairs its secretion. Invest Ophthalmol Vis Sci. 2006;47:5505-13 pubmed
    ..CTRP5, a secretory and membrane-associated protein, is localized to the lateral and apical membranes of the RPE and CB. Impaired secretion of the mutant protein may underlie the pathophysiology of L-ORD and LAZ. ..
  27. Ebrahem Q, Qi J, Sugimoto M, Ali M, Sears J, Cutler A, et al. Increased neovascularization in mice lacking tissue inhibitor of metalloproteinases-3. Invest Ophthalmol Vis Sci. 2011;52:6117-23 pubmed publisher
  28. 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 is only ..
  29. Bian J, Jacobs C, Wang Y, Sun Y. Characterization of a putative p53 binding site in the promoter of the mouse tissue inhibitor of metalloproteinases-3 (TIMP-3) gene: TIMP-3 is not a p53 target gene. Carcinogenesis. 1996;17:2559-62 pubmed
    ..0 microg of dI/dC), T3SF did weakly bind to p53. Lastly, the compounds that induce p53 transactivation activity did not induce TIMP-3 expression. We concluded from this study that TIMP-3 is not a p53 downstream effector gene. ..
  30. Leco K, Edwards D, Schultz G. Tissue inhibitor of metalloproteinases-3 is the major metalloproteinase inhibitor in the decidualizing murine uterus. Mol Reprod Dev. 1996;45:458-65 pubmed
    ..These results support the hypothesis that MMP-9 is an important mediator of cellular invasiveness during embryo implantation, and that TIMP-3 serves as a regulator within the uterus to restrict invasion to the site of implantation. ..
  31. Gill S, Pape M, Leco K. Tissue inhibitor of metalloproteinases 3 regulates extracellular matrix--cell signaling during bronchiole branching morphogenesis. Dev Biol. 2006;298:540-54 pubmed
    ..We examined lungs from TIMP3 null mice and found decreased bronchiole branching, enhanced activity of MMPs and enhanced fibronectin degradation ..
  32. Gill S, Pape M, Leco K. Absence of tissue inhibitor of metalloproteinases 3 disrupts alveologenesis in the mouse. Dev Growth Differ. 2009;51:17-24 pubmed publisher
    ..We examined lungs from TIMP3 null mice and found significant air space enlargement compared with wild type (WT) animals during a time course ..
  33. Inderdeo D, Edwards D, Han V, Khokha R. Temporal and spatial expression of tissue inhibitors of metalloproteinases during the natural ovulatory cycle of the mouse. Biol Reprod. 1996;55:498-508 pubmed
    ..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. ..
  34. Fogarasi M, Janssen A, Weber B, Stohr H. Molecular dissection of TIMP3 mutation S156C associated with Sorsby fundus dystrophy. Matrix Biol. 2008;27:381-92 pubmed publisher
    ..SFD is caused by mutations in the gene encoding the ECM-associated tissue inhibitor of metalloproteases-3 (TIMP3)...
  35. Adissu H, McKerlie C, Di Grappa M, Waterhouse P, Xu Q, Fang H, et al. Timp3 loss accelerates tumour invasion and increases prostate inflammation in a mouse model of prostate cancer. Prostate. 2015;75:1831-43 pubmed publisher
    ..An important negative regulator of protease activity is TIMP3 (tissue inhibitor of metalloproteinase 3)...
  36. Jackson H, Waterhouse P, Sinha A, Kislinger T, Berman H, Khokha R. Expansion of stem cells counteracts age-related mammary regression in compound Timp1/Timp3 null mice. Nat Cell Biol. 2015;17:217-27 pubmed publisher
    ..Compound Timp1/Timp3 null glands exhibit Notch activation and accelerated gestational differentiation...
  37. Nakajima H, Ito M, Smookler D, Shibata F, Fukuchi Y, Morikawa Y, et al. TIMP-3 recruits quiescent hematopoietic stem cells into active cell cycle and expands multipotent progenitor pool. Blood. 2010;116:4474-82 pubmed publisher
  38. Deshmukh H, Shaver C, Case L, Dietsch M, Wesselkamper S, Hardie W, et al. Acrolein-activated matrix metalloproteinase 9 contributes to persistent mucin production. Am J Respir Cell Mol Biol. 2008;38:446-54 pubmed
    ..Augmentation of hMMP9 activity, in turn, could contribute to persistent excessive mucin production. ..
  39. Gill S, Huizar I, Bench E, Sussman S, Wang Y, Khokha R, et al. Tissue inhibitor of metalloproteinases 3 regulates resolution of inflammation following acute lung injury. Am J Pathol. 2010;176:64-73 pubmed publisher
    b>Tissue inhibitor of metalloproteinases 3 (TIMP3) inhibits not only matrix metalloproteinases but also a disintegrin and metalloproteinase domain family members and thus contributes to controlling diverse processes mediated by proteolysis...
  40. Chin J, Werb Z. Matrix metalloproteinases regulate morphogenesis, migration and remodeling of epithelium, tongue skeletal muscle and cartilage in the mandibular arch. Development. 1997;124:1519-30 pubmed
    ..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). ..
  41. Sun Y, Hegamyer G, Kim H, Sithanandam K, Li H, Watts R, et al. Molecular cloning of mouse tissue inhibitor of metalloproteinases-3 and its promoter. Specific lack of expression in neoplastic JB6 cells may reflect altered gene methylation. J Biol Chem. 1995;270:19312-9 pubmed
  42. Hanaoka Y, Yasuda O, Soejima H, Miyata K, Yamamoto E, Izumiya Y, et al. Tissue inhibitor of metalloproteinase-3 knockout mice exhibit enhanced energy expenditure through thermogenesis. PLoS ONE. 2014;9:e94930 pubmed publisher
    ..Given that TIMP-3 deficiency increases energy expenditure, TIMP-3 may present a novel therapeutic target for preventing metabolic disorders. ..
  43. Martin E, Sheikh T, Leco K, Lewis J, Veldhuizen R. Contribution of alveolar macrophages to the response of the TIMP-3 null lung during a septic insult. Am J Physiol Lung Cell Mol Physiol. 2007;293:L779-89 pubmed
    ..This response may be mediated in part by MMP-7 activity but occurs independently of inflammatory cytokine and/or chemokine concentrations. ..
  44. Casagrande V, Mauriello A, Bischetti S, Mavilio M, Federici M, Menghini R. Hepatocyte specific TIMP3 expression prevents diet dependent fatty liver disease and hepatocellular carcinoma. Sci Rep. 2017;7:6747 pubmed publisher
    ..Tissue inhibitor of metalloproteinase 3 (Timp3) has a role in the pathogenesis of fatty liver disease associated with obesity and is silenced during metabolic ..
  45. 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. ..
  46. Trindade A, Kumar S, Scehnet J, Lopes da Costa L, Becker J, Jiang W, et al. Overexpression of delta-like 4 induces arterialization and attenuates vessel formation in developing mouse embryos. Blood. 2008;112:1720-9 pubmed publisher
    ..These results establish the role of Dll4 in arterial identity determination, and regulation of angiogenesis subject to dose and location. ..
  47. Qi J, Dai G, Luthert P, Chaurasia S, Hollyfield J, Weber B, et al. S156C mutation in tissue inhibitor of metalloproteinases-3 induces increased angiogenesis. J Biol Chem. 2009;284:19927-36 pubmed publisher
    ..Understanding the mechanism(s) by which mutant TIMP-3 can induce abnormal neovascularization provides important insight into the pathophysiology of a number of diseases with increased angiogenesis. ..
  48. Pottier N, Chupin C, Defamie V, Cardinaud B, Sutherland R, Rios G, et al. Relationships between early inflammatory response to bleomycin and sensitivity to lung fibrosis: a role for dipeptidyl-peptidase I and tissue inhibitor of metalloproteinase-3?. Am J Respir Crit Care Med. 2007;176:1098-107 pubmed
  49. Levay A, Peacock J, Lu Y, Koch M, Hinton R, Kadler K, et al. Scleraxis is required for cell lineage differentiation and extracellular matrix remodeling during murine heart valve formation in vivo. Circ Res. 2008;103:948-56 pubmed publisher
    ..Collectively, our studies have identified an in vivo requirement for scx during valvulogenesis and demonstrate its role in cell lineage differentiation and matrix distribution in remodeling valve structures. ..
  50. Mavilio M, Marchetti V, Fabrizi M, Stöhr R, Marino A, Casagrande V, et al. A Role for Timp3 in Microbiota-Driven Hepatic Steatosis and Metabolic Dysfunction. Cell Rep. 2016;16:731-43 pubmed publisher
    ..We find that tissue inhibitor of metalloproteinase 3 knockout (Timp3(-/-)) mice fed a high-fat diet exhibit gut microbiota dysbiosis, an increase in branched chain and aromatic (BCAA) ..
  51. 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. ..
  52. Leco K, Apte S, Taniguchi G, Hawkes S, Khokha R, Schultz G, et al. Murine tissue inhibitor of metalloproteinases-4 (Timp-4): cDNA isolation and expression in adult mouse tissues. FEBS Lett. 1997;401:213-7 pubmed
    ..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. ..
  53. Gao F, Du W, Zafar M, Shafqat R, Jian L, Cai Q, et al. 4-Hydroxyisoleucine ameliorates an insulin resistant-like state in 3T3-L1 adipocytes by regulating TACE/TIMP3 expression. Drug Des Devel Ther. 2015;9:5727-36 pubmed publisher
    ..In vivo, TACE activity is suppressed by tissue inhibitor of metalloproteinase 3 (TIMP3). Agents that can interact with TACE/TIMP3 to improve obesity-related IR would be highly valuable...
  54. Joronen K, Salminen H, Glumoff V, Savontaus M, Vuorio E. Temporospatial expression of tissue inhibitors of matrix metalloproteinases-1, -2 and -3 during development, growth and aging of the mouse skeleton. Histochem Cell Biol. 2000;114:157-65 pubmed
    ..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. ..
  55. Schrimpf C, Xin C, Campanholle G, Gill S, Stallcup W, Lin S, et al. Pericyte TIMP3 and ADAMTS1 modulate vascular stability after kidney injury. J Am Soc Nephrol. 2012;23:868-83 pubmed publisher
    ..with thrombospondin motifs-1 (ADAMTS1) and downregulated its inhibitor, tissue inhibitor of metalloproteinase 3 (TIMP3) in response to injury...
  56. Blankenhorn E, Butterfield R, Rigby R, Cort L, Giambrone D, McDermott P, et al. Genetic analysis of the influence of pertussis toxin on experimental allergic encephalomyelitis susceptibility: an environmental agent can override genetic checkpoints. J Immunol. 2000;164:3420-5 pubmed
    ..Taken together, these results suggest that eae9 controls the effects of PTX in EAE susceptibility, and is capable of overriding the other genetic checkpoints in the pathogenesis of this disease. ..
  57. Teesalu T, Masson R, Basset P, Blasi F, Talarico D. Expression of matrix metalloproteinases during murine chorioallantoic placenta maturation. Dev Dyn. 1999;214:248-58 pubmed
    ..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. ..
  58. Beckers J, Herrmann F, Rieger S, Drobyshev A, Horsch M, Hrabe de Angelis M, et al. Identification and validation of novel ERBB2 (HER2, NEU) targets including genes involved in angiogenesis. Int J Cancer. 2005;114:590-7 pubmed
    ..ERBB2 overexpression suppresses the transcription of antiangiogenic factors (e.g., Sparc, Timp3, Serpinf1) but induces expression of angiogenic factors (e.g., Klf5, Tnfaip2, Sema3c)...
  59. Miller B, Spevak L, Lukashova L, Javaheri B, Pitsillides A, Boskey A, et al. Altered Bone Mechanics, Architecture and Composition in the Skeleton of TIMP-3-Deficient Mice. Calcif Tissue Int. 2017;100:631-640 pubmed publisher
    ..In conclusion, this study suggests that the lack of TIMP-3 is detrimental to bone development and maintenance. ..
  60. 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
  61. Lee Y, Fryer J, Kang H, Crespo Barreto J, Bowman A, Gao Y, et al. ATXN1 protein family and CIC regulate extracellular matrix remodeling and lung alveolarization. Dev Cell. 2011;21:746-57 pubmed publisher
    ..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...
  62. Kim H, Pennie W, Sun Y, Colburn N. Differential functional significance of AP-1 binding sites in the promoter of the gene encoding mouse tissue inhibitor of metalloproteinases-3. Biochem J. 1997;324 ( Pt 2):547-53 pubmed
    ..In summary, we report here that both AP-1 and non-AP-1 elements contribute to activity, with the non-consensus AP-1 site at -720 showing the greatest functional significance among the AP-1 sites. ..
  63. Fedak P, Smookler D, Kassiri Z, Ohno N, Leco K, Verma S, et al. TIMP-3 deficiency leads to dilated cardiomyopathy. Circulation. 2004;110:2401-9 pubmed
    ..Therapeutic restoration of myocardial TIMP-3 may provide a novel approach to limit cardiac remodeling and the progression to failure in patients with dilated cardiomyopathy. ..
  64. 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. ..
  65. Basu R, Lee J, Wang Z, Patel V, Fan D, Das S, et al. Loss of TIMP3 selectively exacerbates diabetic nephropathy. Am J Physiol Renal Physiol. 2012;303:F1341-52 pubmed publisher
    ..Polymorphism in the tissue inhibitor of metalloproteinase-3 (TIMP3) gene, and the ECM-bound inhibitor of matrix metalloproteinases (MMPs), has been linked to diabetic nephropathy in ..
  66. Arpino V, Mehta S, Wang L, Bird R, Rohan M, Pape C, et al. Tissue inhibitor of metalloproteinases 3-dependent microvascular endothelial cell barrier function is disrupted under septic conditions. Am J Physiol Heart Circ Physiol. 2016;310:H1455-67 pubmed publisher
    ..Metalloproteinases can regulate MVEC function through processing of cell surface proteins, and tissue inhibitor of metalloproteinases 3 (TIMP3) regulates metalloproteinase activity in the lung following injury...
  67. Arpino V, Brock M, Gill S. The role of TIMPs in regulation of extracellular matrix proteolysis. Matrix Biol. 2015;44-46:247-54 pubmed publisher
    ..Data on the specific metalloproteinases inhibited by different TIMPs in vivo remains limited and must be the focus of future studies. ..
  68. Grossetete M, Rosenberg G. Tissue inhibitor of matrix metalloproteinases-3 (TIMP-3) lacks involvement in bacterial collagenase-induced intracerebral hemorrhage in mouse. Acta Neurochir Suppl. 2008;105:89-93 pubmed
    ..We were unable to prove the hypothesis that TIMP-3 is involved cell death in CIH in the mouse. ..
  69. Fiorentino L, Cavalera M, Menini S, Marchetti V, Mavilio M, Fabrizi M, et al. Loss of TIMP3 underlies diabetic nephropathy via FoxO1/STAT1 interplay. EMBO Mol Med. 2013;5:441-55 pubmed publisher
    ADAM17 and its inhibitor TIMP3 are involved in nephropathy, but their role in diabetic kidney disease (DKD) is unclear. Diabetic Timp3(-/-) mice showed increased albuminuria, increased membrane thickness and mesangial expansion...
  70. Guyot R, Magre S, Leduque P, le Magueresse Battistoni B. Differential expression of tissue inhibitor of metalloproteinases type 1 (TIMP-1) during mouse gonad development. Dev Dyn. 2003;227:357-66 pubmed
    ..Experiments are now under way to determine to what extent TIMP-1 is a morphogenic gene involved in seminiferous cord formation and development. ..
  71. Sun Y, Hegamyer G, Colburn N. Molecular cloning of five messenger RNAs differentially expressed in preneoplastic or neoplastic JB6 mouse epidermal cells: one is homologous to human tissue inhibitor of metalloproteinases-3. Cancer Res. 1994;54:1139-44 pubmed
  72. Yang Y, Jalal F, Thompson J, Walker E, Candelario Jalil E, Li L, et al. Tissue inhibitor of metalloproteinases-3 mediates the death of immature oligodendrocytes via TNF-?/TACE in focal cerebral ischemia in mice. J Neuroinflammation. 2011;8:108 pubmed publisher
    ..Future studies will be needed to delineate the role of MMP-3 and MMP-9 that were increased in the Timp-3 wild type. ..
  73. Wu I, Moses M. Cloning and expression of the cDNA encoding rat tissue inhibitor of metalloproteinase 3 (TIMP-3). Gene. 1996;168:243-6 pubmed
    ..High-level expression of TIMP-3 was detected in rat kidney, lungs and heart. ..
  74. Defamie V, Sanchez O, Murthy A, Khokha R. TIMP3 controls cell fate to confer hepatocellular carcinoma resistance. Oncogene. 2015;34:4098-108 pubmed publisher
    Inflammation enables human cancers and is a critical promoter of hepatocellular carcinoma (HCC). TIMP3 (Tissue inhibitor of metalloproteinase 3), a natural metalloproteinase inhibitor, controls cytokine and growth factor bioavailability ..
  75. Stöhr R, Cavalera M, Menini S, Mavilio M, Casagrande V, Rossi C, et al. Loss of TIMP3 exacerbates atherosclerosis in ApoE null mice. Atherosclerosis. 2014;235:438-43 pubmed publisher
    Tissue inhibitor of metalloproteinase 3 (TIMP3) is a stromal protein that inhibits the activity of various proteases and receptors...
  76. Limana F, Esposito G, D Arcangelo D, Di Carlo A, Romani S, Melillo G, et al. HMGB1 attenuates cardiac remodelling in the failing heart via enhanced cardiac regeneration and miR-206-mediated inhibition of TIMP-3. PLoS ONE. 2011;6:e19845 pubmed publisher
    ..HMGB1 ability to increase miR-206 was confirmed in vitro, in cardiac fibroblasts. TIMP3 was identified as a potential miR-206 target by TargetScan prediction analysis; further, in cultured cardiac ..
  77. 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
  78. Nothnick W, Zhang X, Zhou H. Steroidal regulation of uterine edema and tissue inhibitors of metalloproteinase (TIMP)-3 messenger RNA expression is altered in TIMP-1-deficient mice. Biol Reprod. 2004;70:500-8 pubmed
    ..These observations suggest that steroids induce uterine TIMP-1 expression and, in turn, that TIMP-1 influences TIMP-3 mRNA expression and uterine edema. ..
  79. LU J, Izvolsky K, Qian J, Cardoso W. Identification of FGF10 targets in the embryonic lung epithelium during bud morphogenesis. J Biol Chem. 2005;280:4834-41 pubmed
    ..Our approach identifies Fgf10 targets that are common to multiple biological processes and provides insights into potential mechanisms by which Fgf signaling regulates epithelial cell behavior. ..