Disease relevance of Mmp2

• Rat hepatic stellate cells contribute to the acute-phase response with increased expression of alpha1(I) and alpha1(IV) collagens, tissue inhibitor of metalloproteinase-1, and matrix-metalloproteinase-2 messenger RNAs [1].
• MT1-MMP and gelatinase A were co-localized to sites of active epithelial-mesenchymal transformation and basal lamina disruption in the rat remnant kidney model of progressive renal fibrosis [2].
• Gelatinase A, also denoted matrix metalloproteinase 2, plays multiple critical roles in the neoplastic process, including facilitation of neoangiogenesis and formation of distal metastases [3].
• Transient transfection of hepatocellular carcinoma cell lines with a series of gelatinase A luciferase reporter constructs were in accordance with the binding patterns determined by electrophoretic mobility shift assay [3].
• Interleukin-1beta (IL-1beta), which is increased in the heart following myocardial infarction, increases expression and activity of MMP-2 (gelatinase A) and -9 (gelatinase B) in cardiac fibroblasts [4].

Psychiatry related information on Mmp2

• In particular we investigated MMPI, MMP2 and MMP9 [5].
• Long-term alcohol consumption increases matrix metalloproteinase-2 activity in rat aorta [6].

High impact information on Mmp2

• CONCLUSIONS: Monocrotaline causes depolymerization of F-actin in sinusoidal endothelial cells, which leads to increased expression of metalloproteinase-9 and matrix metalloproteinase-2 by sinusoidal endothelial cells [7].
• In vitro studies of sinusoidal endothelial cells, hepatocytes, stellate cells, and Kupffer cells showed that sinusoidal endothelial cells are the major source of both basal and monocrotaline-induced matrix metalloproteinase-9/matrix metalloproteinase-2 activity [7].
• Inhibition of matrix metalloproteinase-9 and matrix metalloproteinase-2 prevents the development of sinusoidal obstruction syndrome, establishing that matrix metalloproteinase inhibitors may be a therapeutically viable strategy for prevention [7].
• Migration induced by PDGF-BB, TGF-beta1, and collagen I could be inhibited by alpha(1)- and/or alpha(2)-integrin blocking antibodies, collectively suggesting an integrin-dependent, MMP-2-mediated migration of HSCs [8].
• RESULTS: Captopril treatment significantly reduced hepatic hydroxyproline levels, mean fibrosis score, steady state messenger RNA levels of TGF-beta1 and procollagen alpha1(I), and matrix metalloproteinase 2 and 9 activity [9].

Chemical compound and disease context of Mmp2

• Effects of hypoxia, hyperoxia on the regulation of expression and activity of matrix metalloproteinase-2 in hepatic stellate cells [10].
• Long-term overexpression of membrane type-1 matrix metalloproteinase and matrix metalloproteinase-2 in oleic acid-induced pancreatitis in rats [11].
• Benazepril could exert protective effects on diabetic nephropathy, owing to the upregulation of MMP-2 and downregulation of TIMP-2 expressions, which further inhibits the excessive deposition of extracellular matrix in the glomerulus [12].
• However, bosentan decreased pro and active MMP-2 activity in senescent SHR rats, indicating that ET modulates late events in vascular remodelling in hypertension [13].
• CONCLUSIONS: L-arginine attenuates APE-induced pulmonary hypertension through mechanisms involving increased NO synthesis and maybe attenuation of lung MMP-2 and MMP-9 activities [14].

Biological context of Mmp2

• Incubating cells with the antioxidants N-acetylcysteine or ebselen or the MEK pathway inhibitors PD98059 and U0126 prior to irradiation abolished the radiation-induced up-regulation of Mmp2 [15].
• Radiation-induced up-regulation of Mmp2 involves increased mRNA stability, redox modulation, and MAPK activation [15].
• On the other hand, islet morphogenesis was impaired when MMP-2 activity was inhibited [16].
• Specific inhibition of MMP-2 activity in vivo may represent an alternate means of ameliorating complex inflammatory processes by affecting the phenotype of the synthesizing cells, per se [17].
• Treatment of cells embedded in the lattice with furin inhibitor attenuated pro-MT1-MMP processing and MMP-2 activation and impeded cell migration and invasion [18].

Anatomical context of Mmp2

• We have previously observed time- and dose-dependent increases in matrix metalloproteinase 2 (Mmp2) protein levels in rat tubule epithelial cells (NRK52E) after irradiation [15].
• We next demonstrated that when E12.5 pancreatic epithelia develop in vitro, MMP-2 is activated in an in vitro model that recapitulates endocrine pancreas development (Miralles, F., P. Czernichow, and R. Scharfmann. 1998. Development. 125: 1017-1024) [16].
• Increased expression of membrane-type matrix metalloproteinase and preferential localization of matrix metalloproteinase-2 to the neointima of balloon-injured rat carotid arteries [19].
• Differential regulation of matrix metalloproteinase-2 and -9 expression and activity in adult rat cardiac fibroblasts in response to interleukin-1beta [4].
• It is concluded that MMP-2 acts directly upon mesangial cells to permit the development of an inflammatory phenotype [17].

Associations of Mmp2 with chemical compounds

• Studies using the transcription inhibitor actinomycin D (ActD) added 24 h after irradiation revealed the t(1/2) of Mmp2 mRNA to be approximately 8 h in control cells [15].
• Both ethanol and its metabolite acetaldehyde increase MMP2 as well as TIMP2 secretion by PSCs [20].
• There was a correlation between the levels of gelatinase A at 3 hours and the sucrose uptake (P<0.05) [21].
• Both of these proteinases were present at the site of LPS injection at 8 h, but MMP-2 was absent [22].
• Terazosin modifies the content of glycosaminoglycans and the activity of matrix metalloproteinase 2 in the rat ventral prostate [23].

Physical interactions of Mmp2

• Together, these results indicate GATA-2 regulation of the MMP-2 promoter in endothelial cells and that the GATA-2 binding domain is sufficient to drive increased activity of the MMP-2 promoter in response to an extracellular matrix stimulus [24].
• Vitronectin receptor (alpha(v)beta(3)) blockade interferes with binding of this integrin to MMP-2 and proteolyzed collagen, thereby reducing cell invasion [25].

Regulatory relationships of Mmp2

• Treatment of HSCs with concanavalin A (con A) induced activation of MT1-MMP and enhanced secretion of activated gelatinase A, which reached a maximum of 44.4% of the total enzyme secreted into culture supernatants using 30 microgram/mL con A [26].
• We further studied the mechanisms involved in the regulation of MMP-2 mRNA levels and found that the AP-2 transcription factor is responsible for most of the CTGF-induced MMP-2 transcription [27].
• IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression [28].
• Thus, MMP-2-activated TGF-beta1, and subsequently TbetaRII signaling, is a novel molecular mechanism for arterial aging [29].
• Stromelysin-1 and gelatinase A are upregulated before TNF-alpha in LPS-stimulated neuroinflammation [22].

Other interactions of Mmp2

• This effect was specific to MMP-2, because the closely related MMP-9 did not reproduce these changes [17].
• Type I collagen-induced MMP-2 activation coincides with up-regulation of membrane type 1-matrix metalloproteinase and TIMP-2 in cardiac fibroblasts [18].
• Increased MMP-2 expression in connective tissue growth factor over-expression vascular smooth muscle cells [27].
• Upregulation of MMP-2, -8, -9, -13, and -14 and TIMP-1 and TIMP-2 was detected at different timepoints during HF progression [30].
• Expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic stellate cells during rat hepatic fibrosis and its intervention by IL-10 [28].

Analytical, diagnostic and therapeutic context of Mmp2

• Western blotting and gelatin zymography showed an increase in MMP-2 protein levels beginning 5 to 7 days after injury; immunocytochemistry and Western blotting showed that the increase occurred preferentially in the developing neointima [19].
• Northern blot analysis and in situ hybridization showed that, in both pure and co-cultures, HSCs, but not hepatocytes, expressed MMP-2, TIMP-2, and MT-MMP-1 mRNA [31].
• We investigated intermolecular interactions in the gelatinase A activation complex using recombinant proteins, domains, and peptides, yeast two-hybrid analysis, solid- and solution-phase assays, cell culture, and immunocytochemistry [32].
• Increased gelatinase A and B activities were demonstrated in bronchoalveolar lavage [33].
• Zymography analyses revealed the latent form of MMP-2 in medium from 2-day-old pure HSC cultures with higher amounts in medium from hepatocyte/HSC co-cultures [31].

References