TRPV4 channels mediate cardiac fibroblast differentiation by integrating mechanical and soluble signals.

Title

TRPV4 channels mediate cardiac fibroblast differentiation by integrating mechanical and soluble signals.

Creator

Adapala Ravi K; Thoppil Roslin J; Luther Daniel J; Paruchuri Sailaja; Meszaros J Gary; Chilian William M; Thodeti Charles K

Publisher

Journal of molecular and cellular cardiology

Date

2013
2013-01

Description

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-beta 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-beta 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-beta1-induced differentiation of cardiac fibroblasts into myofibroblasts. We found that the TRPV4-specific antagonist AB159908 and siRNA knockdown of TRPV4 significantly inhibited TGFbeta1-induced differentiation as measured by incorporation of alpha-SMA into stress fibers. Further, we found that

Subject

*Calcium Signaling; *Cell Differentiation; *Mechanotransduction; Animals; Cellular; Extracellular Matrix/metabolism/physiology; Fibroblasts/*physiology; Gene Knockdown Techniques; Male; Monoterpenes/pharmacology; Myocardium/cytology; Myofibroblasts/metabolism; Rats; RNA; Small Interfering/genetics; Sprague-Dawley; Transforming Growth Factor beta1/physiology; TRPM Cation Channels/antagonists & inhibitors/metabolism; TRPV Cation Channels/genetics/*metabolism

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

45–52

Volume

54

Citation

Adapala Ravi K; Thoppil Roslin J; Luther Daniel J; Paruchuri Sailaja; Meszaros J Gary; Chilian William M; Thodeti Charles K, “TRPV4 channels mediate cardiac fibroblast differentiation by integrating mechanical and soluble signals.,” NEOMED Bibliography Database, accessed December 4, 2021, https://neomed.omeka.net/items/show/3823.

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