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MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro

Smooth muscle cell (SMC) plasticity plays an important role during development and in vascular pathologies such as atherosclerosis and restenosis. It was recently shown that down-regulation of microRNA (miR)-143 and -145, which are coexpressed from a single promoter, regulates the switch from contra...

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Autores principales: Quintavalle, Manuela, Elia, Leonardo, Condorelli, Gianluigi, Courtneidge, Sara A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854384/
https://www.ncbi.nlm.nih.gov/pubmed/20351064
http://dx.doi.org/10.1083/jcb.200912096
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author Quintavalle, Manuela
Elia, Leonardo
Condorelli, Gianluigi
Courtneidge, Sara A.
author_facet Quintavalle, Manuela
Elia, Leonardo
Condorelli, Gianluigi
Courtneidge, Sara A.
author_sort Quintavalle, Manuela
collection PubMed
description Smooth muscle cell (SMC) plasticity plays an important role during development and in vascular pathologies such as atherosclerosis and restenosis. It was recently shown that down-regulation of microRNA (miR)-143 and -145, which are coexpressed from a single promoter, regulates the switch from contractile to synthetic phenotype, allowing SMCs to migrate and proliferate. We show in this study that loss of miR-143/145 in vitro and in vivo results in the formation of podosomes, which are actin-rich membrane protrusions involved in the migration of several cell types, including SMCs. We further show that platelet-derived growth factor (PDGF) mediates podosome formation in SMCs through the regulation of miR-143/145 expression via a pathway involving Src and p53. Moreover, we identify key podosome regulators as targets of miR-143 (PDGF receptor α and protein kinase C ε) and miR-145 (fascin). Thus, dysregulation of the miR-143 and -145 genes is causally involved in the aberrant SMC plasticity encountered during vascular disease, in part through the up-regulation of an autoregulatory loop that promotes podosome formation.
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spelling pubmed-28543842010-10-05 MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro Quintavalle, Manuela Elia, Leonardo Condorelli, Gianluigi Courtneidge, Sara A. J Cell Biol Research Articles Smooth muscle cell (SMC) plasticity plays an important role during development and in vascular pathologies such as atherosclerosis and restenosis. It was recently shown that down-regulation of microRNA (miR)-143 and -145, which are coexpressed from a single promoter, regulates the switch from contractile to synthetic phenotype, allowing SMCs to migrate and proliferate. We show in this study that loss of miR-143/145 in vitro and in vivo results in the formation of podosomes, which are actin-rich membrane protrusions involved in the migration of several cell types, including SMCs. We further show that platelet-derived growth factor (PDGF) mediates podosome formation in SMCs through the regulation of miR-143/145 expression via a pathway involving Src and p53. Moreover, we identify key podosome regulators as targets of miR-143 (PDGF receptor α and protein kinase C ε) and miR-145 (fascin). Thus, dysregulation of the miR-143 and -145 genes is causally involved in the aberrant SMC plasticity encountered during vascular disease, in part through the up-regulation of an autoregulatory loop that promotes podosome formation. The Rockefeller University Press 2010-04-05 /pmc/articles/PMC2854384/ /pubmed/20351064 http://dx.doi.org/10.1083/jcb.200912096 Text en © 2010 Quintavalle et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Quintavalle, Manuela
Elia, Leonardo
Condorelli, Gianluigi
Courtneidge, Sara A.
MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro
title MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro
title_full MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro
title_fullStr MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro
title_full_unstemmed MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro
title_short MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro
title_sort microrna control of podosome formation in vascular smooth muscle cells in vivo and in vitro
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854384/
https://www.ncbi.nlm.nih.gov/pubmed/20351064
http://dx.doi.org/10.1083/jcb.200912096
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