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JunB Mediates Basal- and TGFβ1-Induced Smooth Muscle Cell Contractility

Smooth muscle contraction is a dynamic process driven by acto-myosin interactions that are controlled by multiple regulatory proteins. Our studies have shown that members of the AP-1 transcription factor family control discrete behaviors of smooth muscle cells (SMC) such as growth, migration and fib...

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Autores principales: Ramachandran, Aruna, Gangopadhyay, Samudra S., Krishnan, Ramaswamy, Ranpura, Sandeep A., Rajendran, Kavitha, Ram-Mohan, Sumati, Mulone, Michelle, Gong, Edward M., Adam, Rosalyn M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537614/
https://www.ncbi.nlm.nih.gov/pubmed/23308222
http://dx.doi.org/10.1371/journal.pone.0053430
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author Ramachandran, Aruna
Gangopadhyay, Samudra S.
Krishnan, Ramaswamy
Ranpura, Sandeep A.
Rajendran, Kavitha
Ram-Mohan, Sumati
Mulone, Michelle
Gong, Edward M.
Adam, Rosalyn M.
author_facet Ramachandran, Aruna
Gangopadhyay, Samudra S.
Krishnan, Ramaswamy
Ranpura, Sandeep A.
Rajendran, Kavitha
Ram-Mohan, Sumati
Mulone, Michelle
Gong, Edward M.
Adam, Rosalyn M.
author_sort Ramachandran, Aruna
collection PubMed
description Smooth muscle contraction is a dynamic process driven by acto-myosin interactions that are controlled by multiple regulatory proteins. Our studies have shown that members of the AP-1 transcription factor family control discrete behaviors of smooth muscle cells (SMC) such as growth, migration and fibrosis. However, the role of AP-1 in regulation of smooth muscle contractility is incompletely understood. In this study we show that the AP-1 family member JunB regulates contractility in visceral SMC by altering actin polymerization and myosin light chain phosphorylation. JunB levels are robustly upregulated downstream of transforming growth factor beta-1 (TGFβ1), a known inducer of SMC contractility. RNAi-mediated silencing of JunB in primary human bladder SMC (pBSMC) inhibited cell contractility under both basal and TGFβ1-stimulated conditions, as determined using gel contraction and traction force microscopy assays. JunB knockdown did not alter expression of the contractile proteins α-SMA, calponin or SM22α. However, JunB silencing decreased levels of Rho kinase (ROCK) and myosin light chain (MLC20). Moreover, JunB silencing attenuated phosphorylation of the MLC20 regulatory phosphatase subunit MYPT1 and the actin severing protein cofilin. Consistent with these changes, cells in which JunB was knocked down showed a reduction in the F:G actin ratio in response to TGFβ1. Together these findings demonstrate a novel function for JunB in regulating visceral smooth muscle cell contractility through effects on both myosin and the actin cytoskeleton.
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spelling pubmed-35376142013-01-10 JunB Mediates Basal- and TGFβ1-Induced Smooth Muscle Cell Contractility Ramachandran, Aruna Gangopadhyay, Samudra S. Krishnan, Ramaswamy Ranpura, Sandeep A. Rajendran, Kavitha Ram-Mohan, Sumati Mulone, Michelle Gong, Edward M. Adam, Rosalyn M. PLoS One Research Article Smooth muscle contraction is a dynamic process driven by acto-myosin interactions that are controlled by multiple regulatory proteins. Our studies have shown that members of the AP-1 transcription factor family control discrete behaviors of smooth muscle cells (SMC) such as growth, migration and fibrosis. However, the role of AP-1 in regulation of smooth muscle contractility is incompletely understood. In this study we show that the AP-1 family member JunB regulates contractility in visceral SMC by altering actin polymerization and myosin light chain phosphorylation. JunB levels are robustly upregulated downstream of transforming growth factor beta-1 (TGFβ1), a known inducer of SMC contractility. RNAi-mediated silencing of JunB in primary human bladder SMC (pBSMC) inhibited cell contractility under both basal and TGFβ1-stimulated conditions, as determined using gel contraction and traction force microscopy assays. JunB knockdown did not alter expression of the contractile proteins α-SMA, calponin or SM22α. However, JunB silencing decreased levels of Rho kinase (ROCK) and myosin light chain (MLC20). Moreover, JunB silencing attenuated phosphorylation of the MLC20 regulatory phosphatase subunit MYPT1 and the actin severing protein cofilin. Consistent with these changes, cells in which JunB was knocked down showed a reduction in the F:G actin ratio in response to TGFβ1. Together these findings demonstrate a novel function for JunB in regulating visceral smooth muscle cell contractility through effects on both myosin and the actin cytoskeleton. Public Library of Science 2013-01-04 /pmc/articles/PMC3537614/ /pubmed/23308222 http://dx.doi.org/10.1371/journal.pone.0053430 Text en © 2013 Ramachandran et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ramachandran, Aruna
Gangopadhyay, Samudra S.
Krishnan, Ramaswamy
Ranpura, Sandeep A.
Rajendran, Kavitha
Ram-Mohan, Sumati
Mulone, Michelle
Gong, Edward M.
Adam, Rosalyn M.
JunB Mediates Basal- and TGFβ1-Induced Smooth Muscle Cell Contractility
title JunB Mediates Basal- and TGFβ1-Induced Smooth Muscle Cell Contractility
title_full JunB Mediates Basal- and TGFβ1-Induced Smooth Muscle Cell Contractility
title_fullStr JunB Mediates Basal- and TGFβ1-Induced Smooth Muscle Cell Contractility
title_full_unstemmed JunB Mediates Basal- and TGFβ1-Induced Smooth Muscle Cell Contractility
title_short JunB Mediates Basal- and TGFβ1-Induced Smooth Muscle Cell Contractility
title_sort junb mediates basal- and tgfβ1-induced smooth muscle cell contractility
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537614/
https://www.ncbi.nlm.nih.gov/pubmed/23308222
http://dx.doi.org/10.1371/journal.pone.0053430
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