Document Detail


TRPV4 channels mediate cardiac fibroblast differentiation by integrating mechanical and soluble signals.
MedLine Citation:
PMID:  23142541     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The phenotypic switch underlying the differentiation of cardiac fibroblasts into hypersecretory myofibroblasts is critical for cardiac remodeling following myocardial infarction. Myofibroblasts facilitate wound repair in the myocardium by secreting and organizing extracellular matrix (ECM) during the wound healing process. However, the molecular mechanisms involved in myofibroblast differentiation are not well known. TGF-β has been shown to promote differentiation and this, combined with the robust mechanical environment in the heart, lead us to hypothesize that the mechanotransduction and TGF-β signaling pathways play active roles in the differentiation of cardiac fibroblasts to myofibroblasts. Here, we show that the mechanosensitve ion channel TRPV4 is required for TGF-β1-induced differentiation of cardiac fibroblasts into myofibroblasts. We found that the TRPV4-specific antagonist AB159908 and siRNA knockdown of TRPV4 significantly inhibited TGFβ1-induced differentiation as measured by incorporation of α-SMA into stress fibers. Further, we found that TGF-β1-induced myofibroblast differentiation was dependent on ECM stiffness, a response that was attenuated by TRPV4 blockade. Finally, TGF-β1 treated fibroblasts exhibited enhanced TRPV4 expression and TRPV4-mediated calcium influx compared to untreated controls. Taken together these results suggest for the first time that the mechanosensitive ion channel, TRPV4, regulates cardiac fibroblast differentiation to myofibroblasts by integrating signals from TGF-β1 and mechanical factors.
Authors:
Ravi K Adapala; Roslin J Thoppil; Daniel J Luther; Sailaja Paruchuri; J Gary Meszaros; William M Chilian; Charles K Thodeti
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-08
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  54     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-06-06     Revised Date:  2014-02-27    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  45-52     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Calcium Signaling*
Cell Differentiation*
Extracellular Matrix / metabolism,  physiology
Fibroblasts / physiology*
Gene Knockdown Techniques
Male
Mechanotransduction, Cellular*
Monoterpenes / pharmacology
Myocardium / cytology
Myofibroblasts / metabolism
RNA, Small Interfering / genetics
Rats
Rats, Sprague-Dawley
TRPM Cation Channels / antagonists & inhibitors,  metabolism
TRPV Cation Channels / genetics,  metabolism*
Transforming Growth Factor beta1 / physiology
Grant Support
ID/Acronym/Agency:
1R15HL106442-01/HL/NHLBI NIH HHS; R15 HL106442/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Monoterpenes; 0/RNA, Small Interfering; 0/TRPM Cation Channels; 0/TRPV Cation Channels; 0/Transforming Growth Factor beta1; 0/Trpv4 protein, rat; 9B1J4V995Q/carvacrol; EC 2.7.11.1/Trpm7 protein, rat
Comments/Corrections
Comment In:
Channels (Austin). 2013 May-Jun;7(3):211-4   [PMID:  23511028 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Optical and electrical recordings from isolated coronary-perfused ventricular wedge preparations.
Next Document:  Tandem mass spectrometry for measuring stable-isotope labeling.