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

By Mei Xin, E. Small, L. Sutherland, X. Qi, John R. McAnally, C. Plato, J. Richardson, R. Bassel-Duby, E. Olson. Genes & Development, 2009

700 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1207d11f13810fb78d3850c7724a846939ad6498

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Molecular Biology

Citations in the corpus

Metazoan MicroRNAs (2018, background): “…et al., 2017) miR-143 (1) miR-143 Arterial smooth muscle defects with perturbed actin stress fibers; less scarring in response to vascular injury (Xin et al., 2009) miR-145 (1) miR-145 Reduced vascular tone with reduced blood pressure; reduced heart mass; arterial smooth muscle defects with…”
The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles. (2012, background): “Consistent with this, smooth muscle miRs are essential for regulating blood pressure levels in resistance vessels,(37) and mice lacking both miR-143 and miR-145 show a significant reduction in blood pressure.(38) In young hypertensive patients, the expression of AT1R is negatively correlated with mi”
MicroRNAs in stress signaling and human disease (2012, background): “This is exemplified by the miR-143/145 cluster, which regulates phenotypic switching of smooth muscle cells (Boettger et al., 2009; Cheng et al., 2009; Cordes et al., 2009; Xin et al., 2009).”
The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and function (2011, unknown): “In vascular smooth muscle cells, miR-143 and miR-145 regulate the switch between differentiated (contractile) and de-differentiated (synthetic or migratory) phenotypes, which occurs in response to vascular stress and injur”
Linking actin dynamics and gene transcription to drive cellular motile functions (2010, unknown): “A screen for miRNAs regulated by MRTF-A in cardiac myocytes identified several miRNAs with key roles in muscle differentiation, proliferation and phenotypic switchin”
MicroRNAs in development and disease. (2011, background): “It is induced by platelet-derived growth factor (PDGF), which is known to stimulate VSMC switching and proliferation during angiogenesis and neointimal formation (133, 378).”
Desperately seeking microRNA targets (2010, background): “Knockout mice lacked gross developmental defects, indicating that the cluster is not essential for developmen”