In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 31, No. 2 ( 2011-02), p. 368-375
Abstract:
Myocardin is a cardiac- and smooth muscle–specific transcription co-factor that potently activates the expression of downstream target genes. Previously, we demonstrated that overexpression of myocardin inhibited the proliferation of smooth muscle cells (SMCs). Recently, myocardin was reported to induce the expression of microRNA-1 (miR-1) in cardiomyocytes. In this study, we investigated whether myocardin induces miR-1 expression to mediate its inhibitory effects on SMC proliferation. Methods and Results— Using tetracycline-regulated expression (T-REx) inducible system expressing myocardin in human vascular SMCs, we found that overexpression of myocardin resulted in significant induction of miR-1 expression and inhibition of SMC proliferation, which was reversed by miR-1 inhibitors. Consistently, introduction of miR-1 into SMCs inhibited their proliferation. We isolated spindle-shaped and epithelioid human SMCs and demonstrated that spindle-shaped SMCs were more differentiated and less proliferative. Correspondingly, spindle-shaped SMCs had significantly higher expression levels of both myocardin and miR-1 than epithelioid SMCs. We identified Pim-1, a serine/threonine kinase, as a target gene for miR-1 in SMCs. Western blot and luciferase reporter assays further confirmed that miR-1 targeted Pim-1 directly. Furthermore, neointimal lesions of mouse carotid arteries displayed downregulation of myocardin and miR-1 with upregulation of Pim-1. Conclusion— Our data demonstrate that miR-1 participates in myocardin-dependent of SMC proliferation inhibition.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/ATVBAHA.110.218149
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2011
detail.hit.zdb_id:
1494427-3
