Genomes and Genes
tissue inhibitor of metalloproteinase 2
Summary: A member of the family of TISSUE INHIBITOR OF METALLOPROTEINASES. It is a 21-kDa nonglycosylated protein found in tissue fluid and is secreted as a complex with progelatinase A by human fibroblast and uncomplexed from alveolar macrophages. An overexpression of TIMP-2 has been shown to inhibit invasive and metastatic activity of tumor cells and decrease tumor growth in vivo.
- Hu Y, Li D, Lu H. Modified synthetic siRNA targeting tissue inhibitor of metalloproteinase-2 inhibits hepatic fibrogenesis in rats. J Gene Med. 2007;9:217-29 pubmed..Knock-down of TIMP-2 expression attenuates CCl4-induced liver fibrosis and is a potential pharmacological target for gene therapy in liver fibrosis. ..
- Muñoz Nájar U, Neurath K, Vumbaca F, Claffey K. Hypoxia stimulates breast carcinoma cell invasion through MT1-MMP and MMP-2 activation. Oncogene. 2006;25:2379-92 pubmed..Our studies suggest that hypoxic tumor microenvironments promote breast cancer invasion through an MT1-MMP-dependent mechanism. ..
- 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. ..
- 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
- Shelton L, Rada J. Effects of cyclic mechanical stretch on extracellular matrix synthesis by human scleral fibroblasts. Exp Eye Res. 2007;84:314-22 pubmed..Increased levels of ActiveMMP-2 in the sclera would be expected to contribute to scleral extracellular matrix degradation, scleral thinning and possible ocular ectasia. ..
- Xiong W, Knispel R, Mactaggart J, Baxter B. Effects of tissue inhibitor of metalloproteinase 2 deficiency on aneurysm formation. J Vasc Surg. 2006;44:1061-6 pubmed..We believe that TIMP-2 promotes aortic enlargement in vivo by activating matrix metalloproteinase 2. ..
- Schippert R, Brand C, Schaeffel F, Feldkaemper M. Changes in scleral MMP-2, TIMP-2 and TGFbeta-2 mRNA expression after imposed myopic and hyperopic defocus in chickens. Exp Eye Res. 2006;82:710-9 pubmed..These changes were confined to the eyes that also displayed reduced growth, suggesting a role of TGFbeta-2 in the final steps of visual eye growth regulation. ..
- Park J, Kim A, Oh J, Chung A. Methylseleninic acid inhibits PMA-stimulated pro-MMP-2 activation mediated by MT1-MMP expression and further tumor invasion through suppression of NF-kappaB activation. Carcinogenesis. 2007;28:837-47 pubmed..Thus, our results suggest that MSeA blocks tumor invasion in vitro via inhibiting pro-MMP-2 activation mediated by suppression of MT1-MMP expression, which is regulated by the NF-kappaB signal pathway. ..
- Graesslin O, Cortez A, Uzan C, Birembaut P, Quereux C, Darai E. Endometrial tumor invasiveness is related to metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expressions. Int J Gynecol Cancer. 2006;16:1911-7 pubmed..These results support the involvement of MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low TIMP-2 expression were the most potent markers of endometrial tumors with a high risk of local and distant spread. ..
- 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
- Kim H, Park C, Park B, Lee H, Jung W. Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in ductal carcinoma in situ and invasive ductal carcinoma of the breast. Yonsei Med J. 2006;47:333-42 pubmed..Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer. ..
- Ries C, Egea V, Karow M, Kolb H, Jochum M, Neth P. MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines. Blood. 2007;109:4055-63 pubmed
- Johnson J, Baker A, Oka K, Chan L, Newby A, Jackson C, et al. Suppression of atherosclerotic plaque progression and instability by tissue inhibitor of metalloproteinase-2: involvement of macrophage migration and apoptosis. Circulation. 2006;113:2435-44 pubmed..Helper-dependent adenovirus technology is required for these effects to be maintained long term. ..
- Zhu H, Zheng J, Xiao X, Zheng S, Dong K, Liu J, et al. Environmental endocrine disruptors promote invasion and metastasis of SK-N-SH human neuroblastoma cells. Oncol Rep. 2010;23:129-39 pubmed..ER-dependent pathway and PI3K/Akt pathway are involved, which may become potential therapeutic targets for neuroblastoma treatment. ..
- Offenberg H, Brunner N, Mansilla F, Orntoft Torben F, Birkenkamp Demtroder K. TIMP-1 expression in human colorectal cancer is associated with TGF-B1, LOXL2, INHBA1, TNF-AIP6 and TIMP-2 transcript profiles. Mol Oncol. 2008;2:233-40 pubmed publisher..These insights add to the complex picture emerging about the regulation of TIMPs in colorectal cancer. ..
- Smyth A, Reid H, Baker A, McGlynn H. Modifications of the radiosensitivity of a renal cancer cell line as a consequence of stable TIMP-1 overexpression. Int J Radiat Biol. 2007;83:13-25 pubmed..05). These results demonstrate a dual role for the TIMP-1 overexpression in this renal carcinoma cell line, both as radiosensitizing agents and effectors of MMP-2 and MMP-9 activity. ..
- Taranta Janusz K, Zoch Zwierz W, Wasilewska A, Tenderenda E, Korzeniecka Kozerska A. [Serum and urinary concentration of selected metalloproteinases and their tissue inhibitors in children with vesicoureteral reflux]. Pol Merkur Lekarski. 2010;29:88-92 pubmed
- Justulin L, Acquaro C, Carvalho R, Silva M, Felisbino S. Combined effect of the finasteride and doxazosin on rat ventral prostate morphology and physiology. Int J Androl. 2010;33:489-99 pubmed publisher..Our results contribute to a better understanding of the clinical data and also of the molecular mechanisms behind isolated or combined Fin and Dox long-term treatment. ..
- Nareika A, Sundararaj K, Im Y, Game B, Lopes Virella M, Huang Y. High glucose and interferon gamma synergistically stimulate MMP-1 expression in U937 macrophages by increasing transcription factor STAT1 activity. Atherosclerosis. 2009;202:363-71 pubmed publisher..In summary, this study revealed a novel mechanism potentially involved in diabetes-promoted cardiovascular disease. ..
- Brun J, Galant C, Delvaux D, Lemoine P, Henriet P, Courtoy P, et al. Menstrual activity of matrix metalloproteinases is decreased in endometrium regenerating after thermal ablation. Hum Reprod. 2009;24:333-40 pubmed publisher..This represents the first molecular explanation for the decreased amount of menstrual bleeding. ..
- Zhu Y, Valter K, Stone J. Environmental damage to the retina and preconditioning: contrasting effects of light and hyperoxic stress. Invest Ophthalmol Vis Sci. 2010;51:4821-30 pubmed publisher..These data suggest a separation between stress-induced damage to photoreceptors and the upregulation of protective mechanisms, encouraging the search for ways to protect the retina without damaging it. ..
- Faure C, Vico L, Tracqui P, Laroche N, Vanden Bossche A, Linossier M, et al. Functionalization of matrices by cyclically stretched osteoblasts through matrix targeting of VEGF. Biomaterials. 2010;31:6477-84 pubmed publisher..05 Hz). This study qualifies high frequency cyclic stretch as an interesting approach for surfaces activation of deformable biomaterials. ..
- Ferrè S, Baldoli E, Leidi M, Maier J. Magnesium deficiency promotes a pro-atherogenic phenotype in cultured human endothelial cells via activation of NFkB. Biochim Biophys Acta. 2010;1802:952-8 pubmed publisher..These results indicate that low magnesium promotes endothelial dysfunction by inducing pro-inflammatory and pro-atherogenic events. ..
- Mitra A, Chakrabarti J, Banerji A, Chatterjee A, Das B. Curcumin, a potential inhibitor of MMP-2 in human laryngeal squamous carcinoma cells HEp2. J Environ Pathol Toxicol Oncol. 2006;25:679-90 pubmed..Reduction of MMP-2 activity and inhibition of HEp2 cell invasion by curcumin strongly indicate the potential of curcumin as an inhibitor of tumor cell invasion and metastasis. ..
- Stetler Stevenson W. The tumor microenvironment: regulation by MMP-independent effects of tissue inhibitor of metalloproteinases-2. Cancer Metastasis Rev. 2008;27:57-66 pubmed..These new findings are discussed in terms of a model of TIMP-2 regulation of cellular functions in the tumor microenvironment. ..
- Shahin A, Elsawaf A, Ramadan S, Shaker O, Amin M, Taha M. Serum levels of tissue inhibitors of metalloproteinase 2 in patients with systemic sclerosis with duration more than 2 years: correlation with cardiac and pulmonary abnormalities. Mediators Inflamm. 2006;2006:38458 pubmed..Our research, though involving a small group of patients, points to the probable role of TIMP-2 in the development of pulmonary lesions in dSSc patients and cardiac lesions in lSSc patients with duration equal to or more than 2 years. ..
- Zeni P, Doepker E, Schulze Topphoff U, Huewel S, Tenenbaum T, Galla H. MMPs contribute to TNF-alpha-induced alteration of the blood-cerebrospinal fluid barrier in vitro. Am J Physiol Cell Physiol. 2007;293:C855-64 pubmed..Thus TNF-alpha may mediate the binding of leukocytes to cellular adhesion molecules and the transmigration across the blood-CSF barrier. ..
- Karamichos D, Brown R, Mudera V. Collagen stiffness regulates cellular contraction and matrix remodeling gene expression. J Biomed Mater Res A. 2007;83:887-94 pubmed..HNFFs did not show any significant changes in these gene expressions indicating a lineage specific response. ..
- Falcinelli E, Giannini S, Boschetti E, Gresele P. Platelets release active matrix metalloproteinase-2 in vivo in humans at a site of vascular injury: lack of inhibition by aspirin. Br J Haematol. 2007;138:221-30 pubmed..In conclusion, MMP-2 is released from platelets in vivo in humans at a localised site of vessel wall damage in amounts sufficient to potentiate platelet aggregation; aspirin does not reduce this release. ..
- Lockwood C, Oner C, Uz Y, Kayisli U, Huang S, Buchwalder L, et al. Matrix metalloproteinase 9 (MMP9) expression in preeclamptic decidua and MMP9 induction by tumor necrosis factor alpha and interleukin 1 beta in human first trimester decidual cells. Biol Reprod. 2008;78:1064-72 pubmed publisher..At the implantation site, inflammatory cytokine-enhanced MMP9 may promote preeclampsia by disrupting the decidual ECM to interfere with normal stepwise EVT invasion. ..
- Selvais C, Gaide Chevronnay H, Lemoine P, Dedieu S, Henriet P, Courtoy P, et al. Metalloproteinase-dependent shedding of low-density lipoprotein receptor-related protein-1 ectodomain decreases endocytic clearance of endometrial matrix metalloproteinase-2 and -9 at menstruation. Endocrinology. 2009;150:3792-9 pubmed publisher
- Ghanei M, Ghalejooghi N, Nourani M, Harandi A, Fooladi A. Effect of TGFß1 and TIMP2 on disease activity in asthma and COPD. Iran J Allergy Asthma Immunol. 2010;9:79-86 pubmed publisher..Furthermore TGFBeta1 may be served as a biomarker in sputum for assessing disease activity and evidence based prescribing corticosteroids in patients with COPD and asthma. ..
- Rajagopalan R, Sridharana S, Menon V. Hepatoprotective role of bis-demethoxy curcumin analog on the expression of matrix metalloproteinase induced by alcohol and polyunsaturated fatty acid in rats. Toxicol Mech Methods. 2010;20:252-9 pubmed publisher..From this study, it is concluded that BDMC-A influences MMPs, TIMPs expression, and acts as an efficient anti-fibrotic agent. ..
- Yamashita M, Yamauchi K, Chiba R, Iwama N, Date F, Shibata N, et al. The definition of fibrogenic processes in fibroblastic foci of idiopathic pulmonary fibrosis based on morphometric quantification of extracellular matrices. Hum Pathol. 2009;40:1278-87 pubmed publisher..Lymphangiogenesis was undetected in all the 3 stages. Thus, pathologic staging helps understand the roles of the factors involved in tissue remodeling in idiopathic pulmonary fibrosis. ..
- Hlawaty H, San Juan A, Jacob M, Vranckx R, Letourneur D, Feldman L. Local matrix metalloproteinase 2 gene knockdown in balloon-injured rabbit carotid arteries using nonviral-small interfering RNA transfection. J Gene Med. 2009;11:92-9 pubmed publisher..No effect was observed on MMP9, pro-MMP9 and TIMP-2 levels. The results obtained in the present study suggest that significant inhibition of gene expression can be achieved with local delivery of siRNA in the arterial wall in vivo. ..
- 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. ..
- Murata K, Kamata Y, Munakata H, Sugai M, Sasaki M. Immunohistochemical study on liver fibrosis in biliary atresia. Hepatogastroenterology. 2008;55:179-83 pubmed..The present study gave a different result than other reports on adult liver fibrosis. Livers with BA may be in a predominant state of fibrolysis, indicating the presence of the similar process to recovery from liver fibrosis in adults. ..
- Salata I, Stojanovic N, Cajdler Łuba A, Lewandowski K, Lewinski A. Gelatinase A (MM-2), gelatinase B (MMP-9) and their inhibitors (TIMP 1, TIMP-2) in serum of women with endometriosis: Significant correlation between MMP-2, MMP-9 and their inhibitors without difference in levels of matrix metalloproteinases and tiss. Gynecol Endocrinol. 2008;24:326-30 pubmed publisher
- Vairaktaris E, Yapijakis C, Yiannopoulos A, Vassiliou S, Serefoglou Z, Vylliotis A, et al. Strong association of the tissue inhibitor of metalloproteinase-2 polymorphism with an increased risk of oral squamous cell carcinoma in Europeans. Oncol Rep. 2007;17:963-8 pubmed..These results indicate that this polymorphism could serve as a genetic marker for the susceptibility of cancer in the oral cavity. ..
- Moon S, Linthicum F, Yang H, Lee S, Park K. Activities of matrix metalloproteinases and tissue inhibitor of metalloproteinase-2 in idiopathic hemotympanum and otitis media with effusion. Acta Otolaryngol. 2008;128:144-50 pubmed..MMP-3 and MMP-7 activity was detected only in the mucous effusions. MMP-9 exhibited activity in all effusions, with the highest levels in mucous effusions. TIMP-2 levels were markedly elevated in serous effusions. ..
- Kliem H, Welter H, Kraetzl W, Steffl M, Meyer H, Schams D, et al. Expression and localisation of extracellular matrix degrading proteases and their inhibitors during the oestrous cycle and after induced luteolysis in the bovine corpus luteum. Reproduction. 2007;134:535-47 pubmed..MMP-2 showed a strong increase in staining in endothelial cells at 48 h. ..
- Zhang Y, Li W, Chi H, Chen J, DenBesten P. JNK/c-Jun signaling pathway mediates the fluoride-induced down-regulation of MMP-20 in vitro. Matrix Biol. 2007;26:633-41 pubmed..These in vitro findings suggest that c-Jun is a key regulatory element for MMP-20 expression, and human ameloblast lineage cells can respond to fluoride by down-regulating MMP-20 transcription through the JNK/c-Jun signaling pathway. ..
- Tenderenda E, Zoch Zwierz W, Wasilewska A, Porowski T, Taranta Janusz K, Kołodziejczyk Z, et al. [Matrix metalloproteinases 2 and 9 and their tissue inhibitors 1 and 2 in the urine of children with pyelonephritis]. Pol Merkur Lekarski. 2009;27:10-3 pubmed..However MMP-2/TIMP-2 ratio was normal. In children with PN the balance MMP-9/TIMP-1 is disturbed, with the predominance of TIMP-1 production over MMP-9. It may lead to renal fibrosis. ..
- O Kane C, McKeown S, Perkins G, Bassford C, Gao F, Thickett D, et al. Salbutamol up-regulates matrix metalloproteinase-9 in the alveolar space in the acute respiratory distress syndrome. Crit Care Med. 2009;37:2242-9 pubmed publisher..We hypothesized that salbutamol reduces MMP activity in ARDS...
- Deng X, He G, Levine A, Cao Y, Mullins C. Adenovirus-mediated expression of TIMP-1 and TIMP-2 in bone inhibits osteolytic degradation by human prostate cancer. Int J Cancer. 2008;122:209-18 pubmed
- Zhang W, Song F, Windsor L. Cigarette smoke condensate affects the collagen-degrading ability of human gingival fibroblasts. J Periodontal Res. 2009;44:704-13 pubmed publisher..Cigarette smoke condensate can increase the collagen-degrading ability of human gingival fibroblasts by altering the production and localization of MMPs and TIMPs. ..
- Christopoulos T, Papageorgakopoulou N, Ravazoula P, Mastronikolis N, Papadas T, Theocharis D, et al. Expression of metalloproteinases and their tissue inhibitors in squamous cell laryngeal carcinoma. Oncol Rep. 2007;18:855-60 pubmed
- Hilska M, Roberts P, Collan Y, Laine V, Kössi J, Hirsimäki P, et al. Prognostic significance of matrix metalloproteinases-1, -2, -7 and -13 and tissue inhibitors of metalloproteinases-1, -2, -3 and -4 in colorectal cancer. Int J Cancer. 2007;121:714-23 pubmed..Different biologic behavior or different genetic development may explain the differences between colon and rectal cancers regarding the expression of MMP-2, TIMP-3 and TIMP-4. ..
- Figueira R, Gomes L, Neto J, Silva F, Silva I, Sogayar M. Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential. BMC Cancer. 2009;9:20 pubmed publisher..Therefore, the multi-factorial analysis of these molecules could provide new and independent prognostic information contributing to the determination of more adequate therapy strategies for each patient. ..
- Swellam M, Arab L, Bushnak H. Clinical implications of HER-2/neu overexpression and proteolytic activity imbalance in breast cancer. IUBMB Life. 2007;59:394-401 pubmed..Thus, the investigated markers are constructive for biologic aggressiveness of breast cancer and MMP-2/TIMP-2 ratio might be a new significant marker in early diagnosis and estimate prognosis in breast cancer. ..
- Cohen M, Schimmel D, Masuda K, Hastings H, Muehleman C. Structural and biochemical evaluation of the elbow capsule after trauma. J Shoulder Elbow Surg. 2007;16:484-90 pubmed..This study demonstrates pathologic thickening, disorganization of the collagen fiber arrangement, and involvement of cytokines in the pathology of post-traumatic contracture of the elbow...
- Li Q, Wang Y, Sun S, Tian Y, Liu M. Effects of benazepril on cardiac fibrosis in STZ-induced diabetic rats. Acta Cardiol. 2010;65:431-9 pubmed..The imbalance of MMP-2 and TIMP-2 expressions in heart tissues might participate in interstitial fibrosis in diabetic myocardiopathy. Benazepril may ameliorate cardiac fibrosis partly by regulating the MMP-2/TIMP-2 system. ..
- Belo V, Souza Costa D, Lana C, Caputo F, Marcaccini A, Gerlach R, et al. Assessment of matrix metalloproteinase (MMP)-2, MMP-8, MMP-9, and their inhibitors, the tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in obese children and adolescents. Clin Biochem. 2009;42:984-90 pubmed publisher..The increased MMP-8 levels found in obese children suggest a possibly relevant pathophysiological mechanism that may be involved in the increase of cardiovascular risk associated with childhood obesity. ..