Document Detail

Paradigmatic identification of MMP-2 and MT1-MMP activation systems in cardiac fibroblasts cultured as a monolayer.
MedLine Citation:
PMID:  15534869     Owner:  NLM     Status:  MEDLINE    
Activations of MMP-2 and membrane type 1-matrix metalloproteinase (MT1-MMP) have been correlated with cell migration, a key cellular event in the wound healing and tissue remodeling. We have previously demonstrated furin-dependent MMP-2 and MT1-MMP activations induced by type I collagen in cardiac fibroblasts. To understand mechanistic aspects of the regulation of MMP-2 and MT1-MMP activations by potential non-matrix factor(s) in cardiac fibroblasts, in the present study, we examined the effects of various agents including concanavalin A (ConA), a proteolytic phenotype-producing agent. We showed that treatment of cells with ConA activated pro-MMP-2, and that this activation concurred with elevated levels of cellular MT1-MMP and TIMP-2. The presence of active MT1-MMP and 43 and 36 kDa processed forms of MT1-MMP in a fraction of intracellular proteins prepared from ConA-treated cells suggests the possible internalization of differential forms of MT1-MMP. The appearance of 36 kDa processed form of MT1-MMP in conditioned media prepared from ConA-treated cells indicates the possible extracellular release of the further processed MT1-MMP fragment. Inhibition of furin in ConA-treated cells attenuated pro-MT1-MMP processing and the cellular TIMP-2 level, plus it reduced cell-released active MMP-2 in a time-dependent manner. These results suggest the involvement of furin in the ConA-induced activations of MT1-MMP and MMP-2. Furthermore, the existence of furin inhibitor-insensitive pro- and active MMP-2 species associated with ConA-treated cells implies that a mechanism independent of furin may perhaps account for the binding of the MMP-2 species to the cells. Supplementary material for this article can be found at
Chun Guo; Juwei Jiang; J Martin Elliott; Lucia Piacentini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  94     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-01-26     Completed Date:  2005-08-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  446-59     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Wiley-Liss, Inc.
Leicester School of Pharmacy, De Montfort University, Leicester, LE1 9BH, UK.
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MeSH Terms
Cells, Cultured
Furin / antagonists & inhibitors
Matrix Metalloproteinase 2 / metabolism*
Matrix Metalloproteinases, Membrane-Associated
Metalloendopeptidases / metabolism*
Myocardium / cytology,  enzymology*
Tissue Inhibitor of Metalloproteinase-2 / metabolism
Reg. No./Substance:
127497-59-0/Tissue Inhibitor of Metalloproteinase-2; EC; EC 3.4.24.-/Matrix Metalloproteinases, Membrane-Associated; EC 3.4.24.-/Metalloendopeptidases; EC Metalloproteinase 2

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