Genomes and Genes
Gene Symbol: TIMP-2
Description: TIMP metallopeptidase inhibitor 2
Alias: CSC-21K, DDC8, metalloproteinase inhibitor 2, testicular secretory protein Li 57, tissue inhibitor of metalloproteinases 2
- Groblewska M, Mroczko B, Gryko M, Kędra B, Szmitkowski M. Matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in the diagnosis of colorectal adenoma and cancer patients. Folia Histochem Cytobiol. 2010;48:564-71 pubmed publisher..Our findings suggest clinical usefulness of TIMP-2 as a biomarker in the diagnosis of CRC, especially in combination with CEA. However, further investigation is necessary. ..
- Park K, Kim S, Kim K, Kim J. Clinical characteristics of TIMP2, MMP2, and MMP9 gene polymorphisms in colorectal cancer. J Gastroenterol Hepatol. 2011;26:391-7 pubmed publisher..005). Specific single-nucleotide polymorphism in TIMP2 and MMP appeared to be associated with tumorigenesis and biological behavior in colorectal cancer, which is expected be further verified in a larger cohort in the future. ..
- Pulukuri S, Patibandla S, Patel J, Estes N, Rao J. Epigenetic inactivation of the tissue inhibitor of metalloproteinase-2 (TIMP-2) gene in human prostate tumors. Oncogene. 2007;26:5229-37 pubmed..These results suggest that the downregulation of the TIMP-2 gene is associated with promoter methylation and that this may play an important role in prostate cancer progression during the invasive and metastatic stages of the disease. ..
- Kubben F, Sier C, Meijer M, Van den Berg M, van der Reijden J, Griffioen G, et al. Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer. Br J Cancer. 2006;95:744-51 pubmed..We conclude that MMP-related SNPs, especially MMP-7(-181A>G) and TIMP-2(303C>T), may be helpful in identifying gastric cancer patients with a poor clinical outcome. ..
- O charoenrat P, Khantapura P. The role of genetic polymorphisms in the promoters of the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 genes in head and neck cancer. Oral Oncol. 2006;42:257-67 pubmed..These findings suggest that the genetic polymorphisms in the promoters of MMP2 and TIMP2 may be associated with the development and aggressiveness of HNSCC. ..
- De Clerck Y, Darville M, Eeckhout Y, Rousseau G. Characterization of the promoter of the gene encoding human tissue inhibitor of metalloproteinases-2 (TIMP-2). Gene. 1994;139:185-91 pubmed..A comparison with the promoter of murine timp-1 revealed several differences consistent with the fact that timp-1 and timp-2 are differentially regulated. ..
- Meersch M, Schmidt C, Van Aken H, Martens S, Rossaint J, Singbartl K, et al. Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS ONE. 2014;9:e93460 pubmed publisher..Urinary [TIMP-2]*[IGFBP7] serves as a sensitive and specific biomarker to predict AKI early after cardiac surgery and to predict renal recovery. www.germanctr.de/, DRKS-ID: DRKS00005062. ..
- Stetler Stevenson W, Seo D. TIMP-2: an endogenous inhibitor of angiogenesis. Trends Mol Med. 2005;11:97-103 pubmed..These new findings are integrated in a comprehensive model of TIMP-2 function in tissue homeostasis. ..
- Srivastava P, Lone T, Kapoor R, Mittal R. Association of promoter polymorphisms in MMP2 and TIMP2 with prostate cancer susceptibility in North India. Arch Med Res. 2012;43:117-24 pubmed publisher..These findings suggested MMP2 variants as a predictor of PCa progression risk among North Indian men. We assume that analysis of these gene polymorphisms can help identify patient subgroups at high risk of poor disease outcome. ..
- Batra J, Soares A, Mehner C, Radisky E. Matrix metalloproteinase-10/TIMP-2 structure and analyses define conserved core interactions and diverse exosite interactions in MMP/TIMP complexes. PLoS ONE. 2013;8:e75836 pubmed publisher..Formation of highly variable exosite interactions may provide a general mechanism by which TIMPs are fine-tuned for distinct regulatory roles in biology. ..
- 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. ..
- Ruokolainen H, Paakko P, Turpeenniemi Hujanen T. Tissue and circulating immunoreactive protein for MMP-2 and TIMP-2 in head and neck squamous cell carcinoma--tissue immunoreactivity predicts aggressive clinical course. Mod Pathol. 2006;19:208-17 pubmed
- Oh J, Diaz T, Wei B, Chang H, Noda M, Stetler Stevenson W. TIMP-2 upregulates RECK expression via dephosphorylation of paxillin tyrosine residues 31 and 118. Oncogene. 2006;25:4230-4 pubmed..Therefore, TIMP-2-mediated inhibition of Src kinase activity leads to the signaling switch from Rac1 to Rap1, thereby leading to enhanced RECK expression. ..
- Kang H, Kim S, Cho B, Kim Y, Hwang Y, Wang K. Single nucleotide polymorphisms of tissue inhibitor of metalloproteinase genes in familial moyamoya disease. Neurosurgery. 2006;58:1074-80; discussion 1074-80 pubmed..Our findings suggest that the presence of a G/C heterozygous genotype at position -418 in TIMP2 promoter could be a genetic predisposing factor for FMMD. ..
- Tuuttila A, Morgunova E, Bergmann U, Lindqvist Y, Maskos K, Fernandez Catalan C, et al. Three-dimensional structure of human tissue inhibitor of metalloproteinases-2 at 2.1 A resolution. J Mol Biol. 1998;284:1133-40 pubmed
- Krex D, Röhl H, Konig I, Ziegler A, Schackert H, Schackert G. Tissue inhibitor of metalloproteinases-1, -2, and -3 polymorphisms in a white population with intracranial aneurysms. Stroke. 2003;34:2817-21 pubmed..These data do not support the hypothesis that genetic variants within these genes have an impact on aneurysm development in the white population. ..
- Chung H, Lee J, Moon H, Hur S, Park M, Wen Y, et al. Matrix metalloproteinase-2, membranous type 1 matrix metalloproteinase, and tissue inhibitor of metalloproteinase-2 expression in ectopic and eutopic endometrium. Fertil Steril. 2002;78:787-95 pubmed..Thus, increased proteolytic activity may help to explain the invasive factors that result in endometriosis. ..
- Bahudhanapati H, Zhang Y, Sidhu S, Brew K. Phage display of tissue inhibitor of metalloproteinases-2 (TIMP-2): identification of selective inhibitors of collagenase-1 (metalloproteinase 1 (MMP-1)). J Biol Chem. 2011;286:31761-70 pubmed publisher..This study suggests that phage display and selection with other MMPs may be an effective method for discovering tissue inhibitor of metalloproteinase variants that discriminate between specified MMPs as targets. ..
- Williamson R, Martorell G, Carr M, Murphy G, Docherty A, Freedman R, et al. Solution structure of the active domain of tissue inhibitor of metalloproteinases-2. A new member of the OB fold protein family. Biochemistry. 1994;33:11745-59 pubmed..Furthermore, the structure has revealed conserved surface regions of potential functional importance. ..
- 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
- Yang L, Gu H, Zhu H, Sun Q, Cong R, Zhou B, et al. Tissue inhibitor of metalloproteinase-2 G-418C polymorphism is associated with an increased risk of gastric cancer in a Chinese population. Eur J Surg Oncol. 2008;34:636-41 pubmed..These findings suggest that the TIMP-2 G-418C polymorphism is a genetic predisposing factor for gastric cancer. ..
- Wu C, Wu M, Chen Y, Chen C, Chen H, Shun C, et al. Clinicopathological significance of MMP-2 and TIMP-2 genotypes in gastric cancer. Eur J Cancer. 2007;43:799-808 pubmed..19, p=0.021), lymphatic invasion (OR=2.87, p=0.016) and venous invasion (OR=2.65, p=0.033). Our results suggest MMP-2 and TIMP-2 genotypes play a crucial role in gastric cancer invasion, but not with development of gastric cancer. ..
- Li X, Kang S, Zhao X, Zhang X, Zhou R, Wang N, et al. [Association of SNPs in the promoter of MMP-2 and TIMP-2 genes with epithelial ovarian cancer]. Yi Chuan. 2008;30:455-62 pubmed..The TIMP-2 G-418C SNP may be associated with the risk of different histological subtypes of epithelial ovarian cancer. ..
- Yang J, Zheng J, Wu L, Shi M, Zhang H, Wang X, et al. NDRG2 ameliorates hepatic fibrosis by inhibiting the TGF-?1/Smad pathway and altering the MMP2/TIMP2 ratio in rats. PLoS ONE. 2011;6:e27710 pubmed publisher..In conclusion, the present findings indicate that the modulation of NDRG2 is a promising strategy for the treatment of liver fibrosis. ..
- Morgunova E, Tuuttila A, Bergmann U, Tryggvason K. Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2. Proc Natl Acad Sci U S A. 2002;99:7414-9 pubmed..This unique structure provides information for how specificity for noninhibitory MMP/TIMP complex formation is achieved. ..
- Yi Y, Chen M, Chen L, Ho E, Ying T, Wang P, et al. Genetic polymorphism of the tissue inhibitor of metalloproteinase-1 is associated with an increased risk of endometrial cancer. Clin Chim Acta. 2009;409:127-31 pubmed publisher..Individuals with TIMP-1_372C/C genotype were at significantly higher risk of endometrial cancer. ..
- Nakopoulou L, Tsirmpa I, Alexandrou P, Louvrou A, Ampela C, Markaki S, et al. MMP-2 protein in invasive breast cancer and the impact of MMP-2/TIMP-2 phenotype on overall survival. Breast Cancer Res Treat. 2003;77:145-55 pubmed..The inverse correlation between MMP-2 and both Ki-67 and p53 can be explained by the potential inhibition of MMP-2 by TIMP-2. These results suggest the necessity of further investigation. ..
- Reuter B, Bugert P, Stroick M, Bukow S, Griebe M, Hennerici M, et al. TIMP-2 gene polymorphism is associated with intracerebral hemorrhage. Cerebrovasc Dis. 2009;28:558-63 pubmed publisher..111). We investigated a SNP 261 base pairs upstream of the start codon in exon 1 of TIMP-2. Our data suggest that carriers of homozygosity for allele A are at increased risk of developing intracerebral hemorrhage. ..
- Brun J, Cortez A, Commo F, Uzan S, Rouzier R, Darai E. Serous and mucinous ovarian tumors express different profiles of MMP-2, -7, -9, MT1-MMP, and TIMP-1 and -2. Int J Oncol. 2008;33:1239-46 pubmed..In conclusion, our results support the differential expression in MMPs and TIMPs of ovarian tumors according to serous or mucinous histology. ..
- Batra J, Robinson J, Soares A, Fields A, Radisky D, Radisky E. Matrix metalloproteinase-10 (MMP-10) interaction with tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2: binding studies and crystal structure. J Biol Chem. 2012;287:15935-46 pubmed publisher..This structural information may ultimately assist in the design of more selective TIMP-based inhibitors tailored for specificity toward individual members of the stromelysin family, with potential therapeutic applications. ..
- Avolio C, Filippi M, Tortorella C, Rocca M, Ruggieri M, Agosta F, et al. Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment. Mult Scler. 2005;11:441-6 pubmed..85; P < 0.05) of the numbers of MRI Gd-TD active lesions. These data confirm that serum MMP-9/TMIP-1 ratio may be viewed as a reliable marker and may be predictive of MRI activity in RR MS. ..
- Munshi H, Wu Y, Mukhopadhyay S, Ottaviano A, Sassano A, Koblinski J, et al. Differential regulation of membrane type 1-matrix metalloproteinase activity by ERK 1/2- and p38 MAPK-modulated tissue inhibitor of metalloproteinases 2 expression controls transforming growth factor-beta1-induced pericellular collagenolysis. J Biol Chem. 2004;279:39042-50 pubmed
- Li H, Zhang Z, Liu W, Yang W, Dong Z, Ma M, et al. Association of a functional polymorphism in the MMP-3 gene with Moyamoya Disease in the Chinese Han population. Cerebrovasc Dis. 2010;30:618-25 pubmed publisher..The findings need to be validated in further studies including more subjects from different populations. ..
- Brehmer B, Biesterfeld S, Jakse G. Expression of matrix metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and -2) in prostate cancer tissue. Prostate Cancer Prostatic Dis. 2003;6:217-22 pubmed..The observed imbalance of MMP and TIMP is mainly caused by a loss of TIMP-1. Furthermore, palpable tumours demonstrated significantly more MMP-2 and significantly less MMP-9 expression than nonpalpable tumours. ..
- Hirano K, Sakamoto T, Uchida Y, Morishima Y, Masuyama K, Ishii Y, et al. Tissue inhibitor of metalloproteinases-2 gene polymorphisms in chronic obstructive pulmonary disease. Eur Respir J. 2001;18:748-52 pubmed
- Urbaniak Kujda D, Kapelko Slowik K, Prajs I, Dybko J, Wolowiec D, Biernat M, et al. Increased expression of metalloproteinase-2 and -9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase-1 and -2 (TIMP-1, TIMP-2), and EMMPRIN (CD147) in multiple myeloma. Hematology. 2016;21:26-33 pubmed publisher..EMMPRIN expression and ratios MMP-9/TIMP-1 and MMP-2/TIMP-2 were higher in MM patients, our results demonstrate that in MM patients MMP-2 and MMP-9 are secreted in higher amounts and are not balanced by inhibitors. ..
- Nikopensius T, Kempa I, Ambrozaityte L, Jagomagi T, Saag M, Matuleviciene A, et al. Variation in FGF1, FOXE1, and TIMP2 genes is associated with nonsyndromic cleft lip with or without cleft palate. Birth Defects Res A Clin Mol Teratol. 2011;91:218-25 pubmed publisher..It is likely that variation in FOXE1, TIMP2, and the FGF and Wnt signaling pathway genes confers susceptibility to nonsyndromic CL/P in Northeastern European populations. ..
- Bojanowska Pozniak K, Kobos J, Gryczyński M, Durko M, Pietruszewska W. [Assessment of tissue inhibitor of metalloproteinases-2 (TIMP-2) in laryngeal cancer]. Otolaryngol Pol. 2007;61:612-6 pubmed publisher..Nevertheless there are more researches needed to explain the role of TIMPs in growth and progression of neoplastic tumors. ..
- Mikołajczyk Stecyna J, Korcz A, Gabriel M, Pawlaczyk K, Oszkinis G, Słomski R. Gene polymorphism -418 G/C of tissue inhibitor of metalloproteinases 2 is associated with abdominal aortic aneurysm. J Vasc Surg. 2015;61:1114-9 pubmed publisher..A decrease in tissue inhibitor of metalloproteinases 2 (TIMP2) gene expression was detected in AAA patients...
- Xiang W, Hu Z, He X, Dang X. Intravenous transfusion of endothelial progenitor cells that overexpress vitamin D receptor inhibits atherosclerosis in apoE-deficient mice. Biomed Pharmacother. 2016;84:1233-1242 pubmed publisher..Taken together, intravenous transfusion of EPCs that overexpress VDR significantly inhibited atherosclerosis in ApoE-deficient mice and could be used as a potential method for angiogenic therapy. ..
- Pantsulaia I, Trofimov S, Kalichman L, Kobyliansky E, Livshits G. The contribution of familial resemblance to variation in circulatory levels of tissue inhibitors of metalloproteinases and transforming growth factor-beta1. Calcif Tissue Int. 2004;74:47-54 pubmed
- Lin X, Chen G, Li C, Zhang L, Shi Y, Zhou D, et al. [Association of polymorphism in matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 with genetic susceptibility of gastric cancer]. Zhonghua Yu Fang Yi Xue Za Zhi. 2011;45:711-6 pubmed..98 and 0.80, P values were 0.81 and 0.85). Polymorphism of TIMP2 is significantly related with occurrence and development of GC and maybe acts as a new biomarker of GC in prognosis. ..
- Wan Z, Li G, Guo Y, Li W, Chen L, Zhang Y. Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury. J Sex Med. 2018;15:304-313 pubmed publisher..Wan Z-H, Li G-H, Guo Y-L, etÂ al. Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury. J Sex Med 2018;15:304-313. ..
- Wang Y, Kong D. LncRNA GAS5 Represses Osteosarcoma Cells Growth and Metastasis via Sponging MiR-203a. Cell Physiol Biochem. 2018;45:844-855 pubmed publisher..LncRNA GAS5 might be a tumor suppressor in osteosarcoma via sponging miR-203a, sequestering miR-203a away from TIMP2. ..
- Klein S, Brandtner A, Lehner G, Ulmer H, Bagshaw S, Wiedermann C, et al. Biomarkers for prediction of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis. Intensive Care Med. 2018;44:323-336 pubmed publisher..Though several biomarkers showed promise and reasonable prediction of RRT use for critically ill patients with AKI, the strength of evidence currently precludes their routine use to guide decision-making on when to initiate RRT. ..
- Theriault B, Woo S, Karimy J, Keledjian K, Stokum J, Sarkar A, et al. Cerebral microbleeds in a neonatal rat model. PLoS ONE. 2017;12:e0171163 pubmed publisher..The study of microbleeds in the neonatal rat brain at full gestation may give insights into the consequences of microbleeds in human preterm infants during critical periods of white matter development. ..
- Su Y, Gong Z, Wu Y, Tian Y, Liao X. Diagnostic Value of Urine Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Acute Kidney Injury: A Meta-Analysis. PLoS ONE. 2017;12:e0170214 pubmed publisher..Urine [TIMP-2]*[IGFBP7] is a promising candidate for early detection of AKI, especially in ruling-out AKI. However, the potential of this biomarker should be validated in larger studies with a broader spectrum of clinical settings. ..
- Bratland A, Ragnhildstveit E, Bjørnland K, Andersen K, Maelandsmo G, Fodstad O, et al. The metalloproteinase inhibitor TIMP-2 is down-regulated by androgens in LNCaP prostate carcinoma cells. Clin Exp Metastasis. 2003;20:541-7 pubmed..Hormonal control of TIMP-2 expression in prostate carcinoma cells has not been previously reported, but whether such regulation has any functional role in the development of osteoblastic metastases in prostate cancer is still unclear. ..
- Lin T, Yang S, Chiu C, Su H, Voon W, Chai C, et al. Mitral tissue inhibitor of metalloproteinase 2 is associated with mitral valve surgery outcome. PLoS ONE. 2014;9:e86287 pubmed publisher..65; p?=?0.003), age (HR 1.05; 95% CI 1.02-1.09; p?=?0.003) and LVESD (HR 1.05; 95% CI 1.01-1.10; p?=?0.020). The lack of mitral TIMP2 expression is associated with increases in cardiovascular death and heart failure following MV surgery. ..
- Park Y, Jeon Y, Kim H, Han I, Oh S, Kim D, et al. The GCâ€‰+â€‰CC genotype at position -418 in TIMP-2 promoter and the -1575GA/-1306CC genotype in MMP-2 is genetic predisposing factors for prevalence of moyamoya disease. BMC Neurol. 2014;14:180 pubmed publisher..Our findings demonstrate that TIMP-2 -418 GCâ€‰+â€‰CC and MMP-2 -1575GA/-1306CC genotypes could be genetic predisposing factors for MMD development. ..
- Koskinen S, Wang W, Ahtikoski A, Kjaer M, Han X, Komulainen J, et al. Acute exercise induced changes in rat skeletal muscle mRNAs and proteins regulating type IV collagen content. Am J Physiol Regul Integr Comp Physiol. 2001;280:R1292-300 pubmed..MMP-2 and TIMP-2 changed only slightly in the white part of MQF and soleus muscle. The changes seem to depend on the severity of myofiber injury and thus probably reflect reorganization of basement membrane compounds...
- Uettwiller Geiger D, Vijayendran R, Kellum J, Fitzgerald R. Analytical characteristics of a biomarker-based risk assessment test for acute kidney injury (AKI). Clin Chim Acta. 2016;455:93-8 pubmed publisher..Our studies demonstrate that the AKIRisk Score has robust analytical performance, good precision, minimal analytical interference, acceptable sensitivity, and excellent sample stability. ..
- Roder C, Peters V, Kasuya H, Nishizawa T, Takehara Y, Berg D, et al. Common genetic polymorphisms in moyamoya and atherosclerotic disease in Europeans. Childs Nerv Syst. 2011;27:245-52 pubmed publisher..Further analyses in larger European cohorts and replication in patients of different ethnicity may lead to possible early detection of patients at risk for developing MMD and subsequently to future causative therapies. ..
- Muskett F, Frenkiel T, Feeney J, Freedman R, Carr M, Williamson R. High resolution structure of the N-terminal domain of tissue inhibitor of metalloproteinases-2 and characterization of its interaction site with matrix metalloproteinase-3. J Biol Chem. 1998;273:21736-43 pubmed
- Ngu J, Teng G, Meijndert H, Mewhort H, Turnbull J, Stetler Stevenson W, et al. Human cardiac fibroblast extracellular matrix remodeling: dual effects of tissue inhibitor of metalloproteinase-2. Cardiovasc Pathol. 2014;23:335-43 pubmed publisher..These observations highlight potential clinical challenges in using TIMP-2 as a therapeutic strategy to attenuate postinjury cardiac remodeling. ..
- Salzmann J, Limb G, Khaw P, Gregor Z, Webster L, Chignell A, et al. Matrix metalloproteinases and their natural inhibitors in fibrovascular membranes of proliferative diabetic retinopathy. Br J Ophthalmol. 2000;84:1091-6 pubmed
- Watanabe M, Hasegawa S, Ohshima N, Tanaka H, Sakamoto T, Sunamori M. Differential regulation of MMP-2, TIMP-2 and IL-6 in valve replacement versus CABG patients. Perfusion. 2002;17:435-9 pubmed..05 versus baseline levels). Plasma MMP-2 concentrations reflect the state of the left ventricle, and changes in plasma MMP-2 and TIMP-2 concentrations during CPB may play an important role in LV remodeling after cardiac surgery. ..
- Matsunaga Y, Koda M, Murawaki Y. Expression of matrix metalloproiteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in hepatocellular carcinoma tissue, compared with the surrounding non-tumor tissue. Res Commun Mol Pathol Pharmacol. 2004;115-116:143-50 pubmed..These findings suggested little association of the clinicopathological findings of HCC with the histological expression of MMPs and TIMPs. ..
- Iochmann S, Blechet C, Chabot V, Saulnier A, Amini A, Gaud G, et al. Transient RNA silencing of tissue factor pathway inhibitor-2 modulates lung cancer cell invasion. Clin Exp Metastasis. 2009;26:457-67 pubmed publisher..In conclusion, this study confirms that TFPI-2 downregulation can contribute to tumour invasion of lung cancer cells. ..
- Nissi R, Talvensaari Mattila A, Kotila V, Niinimäki M, Jarvela I, Turpeenniemi Hujanen T. Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancy failure. Reprod Biol Endocrinol. 2013;11:2 pubmed publisher..The elevated levels of MMP-9 and MMP-2/TIMP-2 complex may play a role in spontaneous termination of pregnancy. ..
- Stetler Stevenson W, Krutzsch H, Liotta L. TIMP-2: identification and characterization of a new member of the metalloproteinase inhibitor family. Matrix Suppl. 1992;1:299-306 pubmed..TIMP-2 produced by tumor cells can also be considered as an onco-suppressor gene product, because it could play an important role in regulating the metalloproteinases involved in tumor invasion and angiogenesis. ..
- Bigg H, Shi Y, Liu Y, Steffensen B, Overall C. Specific, high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP-4) to the COOH-terminal hemopexin-like domain of human gelatinase A. TIMP-4 binds progelatinase A and the COOH-terminal domain in a similar manner to TIMP-2. J Biol Chem. 1997;272:15496-500 pubmed..This new phenomenon may be of important physiological significance in modulating the cell surface activation of progelatinase A. ..
- Sharabi O, Shirian J, Grossman M, Lebendiker M, Sagi I, Shifman J. Affinity- and specificity-enhancing mutations are frequent in multispecific interactions between TIMP2 and MMPs. PLoS ONE. 2014;9:e93712 pubmed publisher..This non-optimality of the binding interface and high potential for improvement might characterize all proteins evolved for binding to multiple targets. ..
- 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
- Özden F, Saygin C, Uzunaslan D, Onal B, Durak H, Aki H. Expression of MMP-1, MMP-9 and TIMP-2 in prostate carcinoma and their influence on prognosis and survival. J Cancer Res Clin Oncol. 2013;139:1373-82 pubmed publisher..Variability of MMP/TIMP expressions from case to case makes it difficult to evaluate their impact on clinical outcome. However, these proteins might be new and promising targets for prostate cancer therapy in the future. ..
- 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. ..