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

Manuela Quintavalle, Leonardo Elia, Gianluigi Condorelli, Sara Courtneidge

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

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)-143and -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 a 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.

Original languageEnglish (US)
Pages (from-to)13-22
Number of pages10
JournalJournal of Cell Biology
Volume189
Issue number1
DOIs
StatePublished - Apr 5 2010
Externally publishedYes

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MicroRNAs
Vascular Smooth Muscle
Smooth Muscle Myocytes
Platelet-Derived Growth Factor Receptors
Platelet-Derived Growth Factor
Vascular Diseases
Protein Kinase C
Cell Movement
Blood Vessels
Podosomes
In Vitro Techniques
Actins
Atherosclerosis
Up-Regulation
Down-Regulation
Pathology
Phenotype
Membranes
Genes

ASJC Scopus subject areas

  • Cell Biology

Cite this

MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro. / Quintavalle, Manuela; Elia, Leonardo; Condorelli, Gianluigi; Courtneidge, Sara.

In: Journal of Cell Biology, Vol. 189, No. 1, 05.04.2010, p. 13-22.

Research output: Contribution to journalArticle

Quintavalle, Manuela ; Elia, Leonardo ; Condorelli, Gianluigi ; Courtneidge, Sara. / MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro. In: Journal of Cell Biology. 2010 ; Vol. 189, No. 1. pp. 13-22.
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