MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury
- 31 August 2009
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 23 (18), 2166-2178
- https://doi.org/10.1101/gad.1842409
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.Keywords
This publication has 53 references indexed in Scilit:
- miR-145 and miR-143 regulate smooth muscle cell fate and plasticityNature, 2009
- Protein kinase D1 regulates cofilin-mediated F-actin reorganization and cell motility through slingshotNature, 2009
- Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosisProceedings of the National Academy of Sciences of the United States of America, 2008
- The Endothelial-Specific MicroRNA miR-126 Governs Vascular Integrity and AngiogenesisDevelopmental Cell, 2008
- Serum response factor micromanaging cardiogenesisCurrent Opinion in Cell Biology, 2007
- MicroRNA Targeting Specificity in Mammals: Determinants beyond Seed PairingMolecular Cell, 2007
- The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2Nature Medicine, 2007
- A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failureProceedings of the National Academy of Sciences of the United States of America, 2006
- A threshold of GATA4 and GATA6 expression is required for cardiovascular developmentProceedings of the National Academy of Sciences of the United States of America, 2006
- Combinatorial microRNA target predictionsNature Genetics, 2005