Document Detail

MMP-2 expression by fibroblasts is suppressed by the myofibroblast phenotype.
MedLine Citation:
PMID:  22449415     Owner:  NLM     Status:  MEDLINE    
During wound healing, fibroblasts transition from quiescence to a migratory state, then to a contractile myofibroblast state associated with wound closure. We found that the myofibroblast phenotype, characterized by the expression of high levels of contractile proteins, suppresses the expression of the pro-migratory gene, MMP-2. Fibroblasts cultured in a 3-D collagen lattice and allowed to develop tension showed increased contractile protein expression and decreased MMP-2 levels in comparison to a stress-released lattice. In 2-D cultures, factors that promote fibroblast contractility, including serum or TGF-β, down-regulated MMP-2. Pharmacologically inducing F-actin disassembly or reduced contractility increased MMP-2 expression, while conditions that promote F-actin assembly suppressed MMP-2 expression. In all cases, changes in MMP-2 levels were inversely related to changes in the contractile marker, smooth muscle α-actin. To determine if the mechanisms involved in contractile protein gene expression play a direct role in MMP-2 regulation, we used RNAi-mediated knock-down of the myocardin-like factors, MRTF-A and MRTF-B, which induced the down-regulation of contractile protein genes by fibroblasts under both serum-containing and serum-free conditions. In the presence of serum or TGF-β, MRTF-A/B knock-down resulted in the up-regulation of MMP-2; serum-free conditions prevented this increased expression. Together, these results indicate that, while MMP-2 expression is suppressed by F-actin formation, its up-regulation is not simply a consequence of contractile protein down-regulation.
Eric W Howard; Beverly J Crider; Dawn L Updike; Elizabeth C Bullen; Eileen E Parks; Carol J Haaksma; David M Sherry; James J Tomasek
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Publication Detail:
Type:  Journal Article     Date:  2012-03-17
Journal Detail:
Title:  Experimental cell research     Volume:  318     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-06-12     Completed Date:  2012-08-24     Revised Date:  2014-10-16    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1542-53     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Actins / chemistry,  metabolism
Cell Culture Techniques / methods
Cell Line
Cell Movement / genetics,  physiology
Fibroblasts / cytology,  enzymology*,  physiology
Gene Expression Regulation, Enzymologic / drug effects
Gene Knockdown Techniques
Insulin-Like Growth Factor I / pharmacology
Matrix Metalloproteinase 2 / genetics*,  metabolism*
Models, Biological
Myofibroblasts / cytology,  enzymology*,  physiology
Protein Multimerization
RNA Interference
Transcription Factors / antagonists & inhibitors,  genetics
Wound Healing / genetics,  physiology
Grant Support
Reg. No./Substance:
0/Actins; 0/Transcription Factors; 0/myocardin-related transcription factor-A, rat; 0/myocardin-related transcription factor-B, rat; 0/smooth muscle actin, rat; 67763-96-6/Insulin-Like Growth Factor I; EC Metalloproteinase 2; EC protein, rat

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