Document Detail

Gene regulation by mechanotransduction in fibroblasts.
MedLine Citation:
PMID:  18059623     Owner:  NLM     Status:  MEDLINE    
Mechanical forces are important for connective tissue homeostasis. How do fibroblasts sense mechanical stress and how do they translate this information into an adaptive remodeling of the extracellular matrix (ECM)? Tenascin-C is rapidly induced in vivo by loading muscles and in vitro by stretching fibroblasts. Regulation of tenascin-C expression by mechanical signals occurs at the transcriptional level. Integrin receptors physically link the ECM to the cytoskeleton and act as force transducers: intracellular signals are triggered when integrins engage with ECM, and later when forces are applied. We found that cyclic strain does not induce tenascin-C messenger ribonucleic acid (mRNA) in fibroblasts lacking the beta1-integrin chain. An important link in integrin-dependent mechanotransduction is the small guanosine 5'-triphosphatase. RhoA and its target kinase, ROCK. In fibroblasts, cyclic strain activates RhoA and thereby induces ROCK-dependent actin assembly. Interestingly, tenascin-C mRNA induction by cyclic strain was suppressed by relaxing the cytoskeleton with a ROCK inhibitor or by actin depolymerization. Conversely, chemical activators of RhoA enhanced the effect of strain both on actin dynamics and on tenascin-C expression. Thus, RhoA/ROCK-controlled actin dynamics are required for the induction of specific ECM genes by mechanical stress. These findings have implications for the understanding of regeneration and for tissue engineering.
Matthias Chiquet; Vildan Tunç-Civelek; Ana Sarasa-Renedo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Applied physiology, nutrition, and metabolism = Physiologie appliquée, nutrition et métabolisme     Volume:  32     ISSN:  1715-5312     ISO Abbreviation:  -     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-12-06     Completed Date:  2008-01-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101264333     Medline TA:  Appl Physiol Nutr Metab     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  967-73     Citation Subset:  IM    
ITI Research Institute for Dental and Skeletal Biology, University of Bern, Murtenstrasse 35, CH-3010 Bern, Switzerland.
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MeSH Terms
Connective Tissue / metabolism
Fibroblasts / metabolism*
Gene Expression Regulation*
Mechanotransduction, Cellular / physiology*

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