Disease relevance of MMP2

• These results show that topical application of mitogenic bovine whey extract was able to modulate the expression of MMP-2, -9, and TIMP-2 in chronic leg ulcers and that its constituent growth factors may have the potential to redress the proteolytic imbalance observed in nonhealing chronic ulcers [1].
• The MMP-2 mRNA level was not significantly affected by IL-1beta in normoxia or hypoxia, whereas it was enhanced in reoxygenated cultures [2].
• In conclusion, these results suggest a significant role of these proteases in growth and development of bovine follicle, particularly proMMP-2 and active MMP-2 activities in the follicular fluid could serve as markers of follicular health while abundance of proMMP-9 may possibly denote a follicular cyst [3].
• Thus, gelatinases, especially MMP-2, are involved in the early degradation of the blood-milk barrier, which precedes the penetration of blood-derived cellular components into milk in endotoxin-induced mastitis [4].
• Role of MMP-2 in PKCdelta-mediated inhibition of Na+ dependent Ca2+ uptake in microsomes of pulmonary smooth muscle: involvement of a pertussis toxin sensitive protein [5].

High impact information on MMP2

• Hence, these findings show that endothelial cell invasion of collagen I gels is MT1-MMP and alpha(v)beta3 - dependent but MMP-2 independent and does not support a role for PEX in alpha(v)beta3 integrin binding or in modulating angiogenesis in this system [6].
• Likewise, integrin alpha(v)beta3 -expressing cells did not bind MMP-2-coated surfaces [6].
• RESULTS: The addition of Dec-RVKR-CH(2)Cl to stimulated cartilage reduced the release of collagen fragments and the levels of active collagenase and MMP-2, suggesting that furin-like enzymes are involved in the cascades leading to activation of procollagenases [7].
• Further testing of this clone demonstrated that the TSR interacted with the NH(2)-terminal region of the MMP2 that contains the catalytic domain [8].
• The low constitutive expression of gelatinase A/MMP-2 was upregulated by TGF-beta1 in a dose-dependent manner [9].

Chemical compound and disease context of MMP2

• Pretreatment with Gialpha-protein inhibitors, pertussis toxin (PTX) and NF023, transient expression of inhibitory mutants of Gialpha-subunits, or pretreatment with RGD peptides to block RGD-dependent integrin signaling failed to attenuate strain-induced increases in MMP-2 expression in BAECs [10].

Biological context of MMP2

• In the present studies, we demonstrated that radiation (10 Gy) induced an immediate increase in the amounts and activation of MMP1 and MMP2 in the cell fraction and medium of bovine capillary endothelial cells followed by an incidence of apoptosis [11].
• Cyclic strain-induced endothelial MMP-2: role in vascular smooth muscle cell migration [12].
• We have recently reported the cloning of bovine membrane-type 1 metalloproteinase (MT1-MMP) and have shown that active MT1-MMP is correlated to MMP-2 activity in the CL during the estrous cycle [13].
• However, the effect on BASMC migration of MMP-2 siRNA transfection in BAECs could be reversed by supplementation of recombinant MMP-2 into BAEC media prior to (and for the duration of) strain [12].
• Bovine MMP-2 cDNA was isolated from a UNI-ZAP II bovine capillary endothelial cell cDNA library and sequenced [13].

Anatomical context of MMP2

• In addition to large luteal cells, MMP2 was localized to endothelial cells in all ages of CL by immunohistochemistry [13].
• Immunohistochemical analysis of ulcer biopsies for MMP-2, -9, and TIMP-2 expression showed a reduction in the number of MMP-2-positive dermal fibroblasts in the mitogenic bovine whey extract-treated ulcers compared with pretreatment biopsies (p<0.05) that persisted over the course of the study [1].
• In this study, we investigated the putative role of cyclic strain-induced endothelial MMP-2 (and MMP-9) expression and release in modulating bovine aortic smooth muscle cell (BASMC) migration in vitro [12].
• The resulting activation of MMP-2 subsequently inhibits Na+ dependent Ca2+ uptake in the microsomes [14].
• We have determined effect of the oxidant peroxynitrite (ONOO-) on Ca2+-dependent matrix metalloprotease-2 (MMP-2) activity and the role of the protease on Ca2+ ATPase activity in bovine pulmonary vascular smooth muscle plasma membrane under ONOO- -triggered conditions [15].

Associations of MMP2 with chemical compounds

• Metalloproteinase (MMP-2) activity was detected in all the samples analyzed but a higher expression of MMP-9 was detected in those implants treated with chloroform/methanol and ethanol [16].
• Moreover, inhibition of strain-mediated MMP-2 expression in BAECs by protein tyrosine kinase (PTK) blockade with genistein (50 microM) was also found to completely reverse this inhibitory effect on BASMC migration [12].
• Since 72 kDa is the molecular mass of MMP-2 and since in our present study the 72 kDa protease in the gelatin containing zymogram is inhibited by matrix metalloprotease inhibitors, EGTA and TIMP-2, it may be suggested that the 72 kDa protease is the MMP-2 [17].
• However, the ONOO- -stimulated MMP-2 activity and the Ca2+ ATPase activity were found to be insensitive to phenylmethylsulfonylfluoride, Bowman-Birk inhibitor, chymostatin, leupeptin, antipain, N-ethylmaleimide, and pepstatin [15].
• Lipopolysaccharide-stimulated alveolar macrophages express MMP-9 but not MMP-2 mRNA [18].

Physical interactions of MMP2

• Heparin-sepharose (100 mM NaCl eluate)-purified preparation contained the MMP-2/TIMP-2 complex [19].
• A binding assay was used to determine the specificity of TSP-1 binding to MMP2 [20].

Regulatory relationships of MMP2

• It was IFN-tau that inhibited the production of MMP-2 [21].
• CONCLUSION: TSP-1 induced MMP2 activation through transcriptional and posttranslational mechanisms [20].
• Among these MMPs, membrane-type MMP-1 (MT1-MMP) is an important molecule that can trigger the invasion of tumor cells by activating MMP-2 on their plasma membrane [22].

Other interactions of MMP2

• Statistical analysis (n = 35) revealed a strong positive correlation among the mRNA levels of several elements of the MMP system, including MMP-2, MMP-14, TIMP-1, -2, and -3 (r = 0.614 to 0.930, P < 0.0001) [23].
• Matrix metalloproteinase-2 (MMP-2) expression and regulation by tumor necrosis factor alpha (TNFalpha) in the bovine corpus luteum [13].
• In order to understand how blastocysts affected MMP-2 production, we examined the effect of progesterone, estradiol, insulin-like growth factors (IGFs), tumor necrosis factors (TNFs), and interferon-tau (IFN-tau) supplementation [21].
• We hypothesized that TSP-1 modulates MMP2 activity in VSMCs and is critical for VSMC migration [20].
• Zymography showed downregulation of MMP-2 and MMP-9 in SMCs exposed to PAI-1 overexpressing EC [24].

Analytical, diagnostic and therapeutic context of MMP2

• Northern and Western blotting revealed that the levels of MMP-2 mRNA (3.1 kb) and immunoreactive pro-MMP-2 protein (68 kDa) did not differ (P > 0.05) in any age of CL examined [13].
• Immunoblotting of BALF protein and conditioned medium confirmed the MMP-2 and -9 proteins [18].
• The homogeneity of the isolated MMP-2 and the complex was demonstrated by SDS-PAGE under nonreducing condition and also by nondenaturing native-PAGE [19].
• MMP2 messenger RNA expression was determined with Northern blot analysis [20].
• Retinal pigment epithelium-associated interphotoreceptor matrix, both unfractionated as well as fractions separated by gel filtration, exhibited bands of proteolytic activity on gelatin-loaded gels at about 70-75 kDa and 90 kDa, possibly due to gelatinases A and B (MMP-2 and MMP-9, respectively) [25].

References