MicroRNA‐1 inhibits myocardin‐induced contractility of human vascular smooth muscle cells

Abstract

Myocardin, a cofactor of serum response factor (SRF), specifically induces the expression of contractile proteins to promote differentiation and contractile phenotype of smooth muscle cells (SMCs). SRF directly induces the transcription of microRNA-1 (miR-1) in cardiac and skeletal muscle precursor cells and miR-1 promotes the skeletal muscle differentiation and modulates cardiac hypertrophy. We aimed to examine whether miR-1 plays a role in the regulation of smooth muscle contractility. We found that miR-1 expression was induced by myocardin overexpression in human aortic SMCs. In a collagen lattice contraction assay using SMCs harboring a doxycycline-inducible expression system for myocardin, we found that myocardin expression increased the contractility of SMCs, which was significantly inhibited by exogenous miR-1. Our further studies revealed that exogenous miR-1, which did not affect myocardin or SRF expression, suppressed the expression of contractile proteins, such as alpha-SMA and SM22, and impaired the actin cytoskeletal organization. Taken together, our results have revealed that myocardin induces miR-1 expression, which represses the expression of contractile proteins and thereby inhibits the contractility of SMCs. Therefore, our findings suggest a role of miR-1 in the negative feedback loop in the regulation of contractility induced by myocardin.

MicroRNA-133 Controls Vascular Smooth Muscle Cell Phenotypic Switch In Vitro and Vascular Remodeling In Vivo

“…The data above are only in part at odds with the findings of our present study. First, the data from Zheng group 12,13 are consistent with our findings in showing minimal if not negligible levels of miR-1 in normal quiescent human SMCs. Second, miR-1 effects on human SMC proliferation are mainly secondary to myocardin overexpression.…”

“…Second, miR-1 effects on human SMC proliferation are mainly secondary to myocardin overexpression. 12,13 Third, in the latter 2 studies, 2 different human SMC lines were obtained through in vitro selection, which may have a role in the reported findings. Finally, it should be noted that we injured carotid vessel by balloon endothelial denudation and media injury which is different from the mouse carotid ligation model used by Chen et al 13 Accordingly, the reduced expression of miR-1 in the vascular wall after carotid ligation cannot be accounted for by specific variation within SMCs, as it may depend on other cell types within the vessel tissue.…”

“…6 -11 More recently, 2 articles demonstrated that miR-1 is induced by myocardin overexpression in human SMCs, contributing to myocardin-dependent reduction of human SMC growth in vitro. 12,13 miR-133a-1/miR-1-2 and miR133a-2/miR-1-1 are 2 bicistronic miRNA clusters reported to be specifically expressed in cardiac and skeletal muscle. 4,5 A third bicistronic miRNA cluster, comprising miR-206 and miR-133b, is expressed specifically in skeletal muscle but not in the heart.…”

Implication of microRNAs in atrial natriuretic peptide and nitric oxide signaling in vascular smooth muscle cells

“…Mice lacking miR-143 and miR-145 develop significant reduction in blood pressure due to reduced vascular tone (68). Myocardininduced miR-1 represses the expression of contractile proteins and thereby inhibits contraction of VSMCs (26). miR-126 regulates angiogenesis (65).…”

Regulation of microRNA expression in vascular smooth muscle by MRTF-A and actin polymerization

“…Similarly, overexpression of miR-1 can inhibit myocardin-induced contractility in human vascular smooth muscle cells [58]. In our screening MiRNA-378a is known to have important functions in both skeletal [61] and cardiac muscle [62], while its role for smooth muscle function remains to be elucidated.…”