Myocardin-Related Transcription Factors-A and -B are Key Regulators of TGF-β1-Induced Fibroblast to Myofibroblast Differentiation

Myofibroblasts are contractile, smooth muscle-like cells that are characterized by the de novo expression of smooth muscle α-actin (SMαA) and normally function to assist in wound closure, but have been implicated in pathological contractures. Transforming growth factor beta-1 (TGF-β1) helps facilita...

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Main Authors:	Crider, Beverly J., Risinger, George M., Haaksma, Carol J., Howard, Eric W., Tomasek, James J.
Format:	Online
Language:	English
Published:	2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199034/

id	pubmed-3199034
recordtype	oai_dc
spelling	pubmed-31990342012-06-01 Myocardin-Related Transcription Factors-A and -B are Key Regulators of TGF-β1-Induced Fibroblast to Myofibroblast Differentiation Crider, Beverly J. Risinger, George M. Haaksma, Carol J. Howard, Eric W. Tomasek, James J. Article Myofibroblasts are contractile, smooth muscle-like cells that are characterized by the de novo expression of smooth muscle α-actin (SMαA) and normally function to assist in wound closure, but have been implicated in pathological contractures. Transforming growth factor beta-1 (TGF-β1) helps facilitate the differentiation of fibroblasts into myofibroblasts, but the exact mechanism by which this differentiation occurs, in response to TGF-β1, remains unclear. Myocardin-related transcription factors-A and -B (MRTFs, MRTF-A/B) are transcriptional co-activators that regulate the expression of smooth muscle-specific cytoskeletal proteins, including SMαA, in smooth muscle cells and fibroblasts. In this study, we demonstrate that TGF-β1 mediates myofibroblast differentiation and the expression of a contractile gene program through the actions of the MRTFs. Transient transfection of a constitutively-active MRTF-A induced an increase in the expression of SMαA and other smooth muscle-specific cytoskeletal proteins, and an increase in myofibroblast contractility, even in the absence of TGF-β1. MRTF-A/B knockdown, in TGF-β1 differentiated myofibroblasts, resulted in decreased smooth muscle-specific cytoskeletal protein expression levels and reduced contractile force generation, as well as a decrease in focal adhesion size and number. These results provide direct evidence that the MRTFs are mediators of myofibroblast differentiation in response to TGF-β1. 2011-07-21 2011-12 /pmc/articles/PMC3199034/ /pubmed/21776010 http://dx.doi.org/10.1038/jid.2011.219 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Crider, Beverly J. Risinger, George M. Haaksma, Carol J. Howard, Eric W. Tomasek, James J.
spellingShingle	Crider, Beverly J. Risinger, George M. Haaksma, Carol J. Howard, Eric W. Tomasek, James J. Myocardin-Related Transcription Factors-A and -B are Key Regulators of TGF-β1-Induced Fibroblast to Myofibroblast Differentiation
author_facet	Crider, Beverly J. Risinger, George M. Haaksma, Carol J. Howard, Eric W. Tomasek, James J.
author_sort	Crider, Beverly J.
title	Myocardin-Related Transcription Factors-A and -B are Key Regulators of TGF-β1-Induced Fibroblast to Myofibroblast Differentiation
title_short	Myocardin-Related Transcription Factors-A and -B are Key Regulators of TGF-β1-Induced Fibroblast to Myofibroblast Differentiation
title_full	Myocardin-Related Transcription Factors-A and -B are Key Regulators of TGF-β1-Induced Fibroblast to Myofibroblast Differentiation
title_fullStr	Myocardin-Related Transcription Factors-A and -B are Key Regulators of TGF-β1-Induced Fibroblast to Myofibroblast Differentiation
title_full_unstemmed	Myocardin-Related Transcription Factors-A and -B are Key Regulators of TGF-β1-Induced Fibroblast to Myofibroblast Differentiation
title_sort	myocardin-related transcription factors-a and -b are key regulators of tgf-β1-induced fibroblast to myofibroblast differentiation
description	Myofibroblasts are contractile, smooth muscle-like cells that are characterized by the de novo expression of smooth muscle α-actin (SMαA) and normally function to assist in wound closure, but have been implicated in pathological contractures. Transforming growth factor beta-1 (TGF-β1) helps facilitate the differentiation of fibroblasts into myofibroblasts, but the exact mechanism by which this differentiation occurs, in response to TGF-β1, remains unclear. Myocardin-related transcription factors-A and -B (MRTFs, MRTF-A/B) are transcriptional co-activators that regulate the expression of smooth muscle-specific cytoskeletal proteins, including SMαA, in smooth muscle cells and fibroblasts. In this study, we demonstrate that TGF-β1 mediates myofibroblast differentiation and the expression of a contractile gene program through the actions of the MRTFs. Transient transfection of a constitutively-active MRTF-A induced an increase in the expression of SMαA and other smooth muscle-specific cytoskeletal proteins, and an increase in myofibroblast contractility, even in the absence of TGF-β1. MRTF-A/B knockdown, in TGF-β1 differentiated myofibroblasts, resulted in decreased smooth muscle-specific cytoskeletal protein expression levels and reduced contractile force generation, as well as a decrease in focal adhesion size and number. These results provide direct evidence that the MRTFs are mediators of myofibroblast differentiation in response to TGF-β1.
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199034/
_version_	1611482686466031616

Myocardin-Related Transcription Factors-A and -B are Key Regulators of TGF-β1-Induced Fibroblast to Myofibroblast Differentiation

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