MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury

Mei Xin, Eric M. Small, Lillian B. Sutherland, Xiaoxia Qi, John McAnally, Craig F. Plato, James A. Richardson, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journalArticle

474 Citations (Scopus)

Abstract

Vascular injury triggers dedifferentiation and cytoskeletal remodeling of smooth muscle cells (SMCs), culminating in vessel occlusion. Serum response factor (SRF) and its coactivator, myocardin, play a central role in the control of smooth muscle phenotypes by regulating the expression of cytoskeletal genes. We show that SRF and myocardin regulate a cardiovascular-specific microRNA (miRNA) cluster encoding miR-143 and miR-145. To assess the functions of these miRNAs in vivo, we systematically deleted them singly and in combination in mice. Mice lacking both miR-143 and miR-145 are viable and do not display overt abnormalities in smooth muscle differentiation, although they show a significant reduction in blood pressure due to reduced vascular tone. Remarkably, however, neointima formation in response to vascular injury is profoundly impeded in mice lacking these miRNAs, due to disarray of actin stress fibers and diminished migratory activity of SMCs. These abnormalities reflect the regulation of a cadre of modulators of SRF activity and actin dynamics by miR-143 and miR-145. Thus, miR-143 and miR-145 act as integral components of the regulatory network whereby SRF controls cytoskeletal remodeling and phenotypic switching of SMCs during vascular disease.

Original languageEnglish (US)
Pages (from-to)2166-2178
Number of pages13
JournalGenes and Development
Volume23
Issue number18
DOIs
StatePublished - Sep 15 2009

Fingerprint

Serum Response Factor
MicroRNAs
Smooth Muscle Myocytes
Vascular System Injuries
Wounds and Injuries
Smooth Muscle
Actins
Neointima
Stress Fibers
Vascular Diseases
Blood Vessels
Blood Pressure
Phenotype
Gene Expression
myocardin

Keywords

  • Actin signaling
  • MicroRNA
  • Myocardin
  • Serum response factor
  • Vascular disease

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. / Xin, Mei; Small, Eric M.; Sutherland, Lillian B.; Qi, Xiaoxia; McAnally, John; Plato, Craig F.; Richardson, James A.; Bassel-Duby, Rhonda; Olson, Eric N.

In: Genes and Development, Vol. 23, No. 18, 15.09.2009, p. 2166-2178.

Research output: Contribution to journalArticle

Xin, Mei ; Small, Eric M. ; Sutherland, Lillian B. ; Qi, Xiaoxia ; McAnally, John ; Plato, Craig F. ; Richardson, James A. ; Bassel-Duby, Rhonda ; Olson, Eric N. / MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. In: Genes and Development. 2009 ; Vol. 23, No. 18. pp. 2166-2178.
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