Down-regulation of mir-542-3p promotes neointimal formation in the aging rat.

Abstract

AIM:

To explore mir-542-3p mediated inhibition of vascular smooth muscle cell (VSMC) proliferation through the inhibition of Syk activation.

METHODS AND RESULTS:

MicroRNA (mir)-542-3p was selected for analysis based on miRNA microarray and qRT-PCR results. In vitro mir-542-3p expression was significantly downregulated in old (o)VSMCs compared with young (y)VSMCs under serum stimulation conditions. Upregulation of mir-542-3p in oVSMCs significantly inhibited VSMC proliferation, whereas downregulation of mir-542-3p in yVSMCs increased VSMC proliferation. We identified spleen tyrosine kinase (Syk) as a direct target of mir-542-3p by database search, and showed that its expression and phosphorylation were higher in oVSMCs than in yVSMCs after serum stimulation. Luciferase assays confirmed that Syk is a direct target of miR-3542-3p. Knock-down of mir-542-3p in yVSMCs inhibited the activation of the Syk downstream effectors STAT3 and STAT5, whereas mir-542-3p overexpression enhanced STAT3 and STAT5 activities. In a rat balloon injury model, mir-542-3p inhibited neointima formation and proliferating cell nuclear antigen (PCNA) protein expression.

CONCLUSION:

Mir-542-3p modulates VSMC proliferation via the Syk/STAT3-STAT5 axis. Downregulation of mir-542-3p may explain age-related neointimal hyperplasia in rats.

• Authors: De-hui Qian, Pan Gao, Huan Feng, Zhe-Xue Qin, Jia-bei Li, Lan Huang
• Journal: Vascular pharmacology (Vascul Pharmacol) Vol. 72 Pg. 118-29 (Sep 2015) ISSN: 1879-3649 [Electronic] United States
• PMID: 26026397 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• MicroRNAs

Topics

• Aging (genetics)
• Animals
• Cell Proliferation (genetics)
• Down-Regulation (genetics)
• Male
• MicroRNAs (genetics)
• Muscle, Smooth, Vascular (metabolism)
• Myocytes, Smooth Muscle (metabolism)
• Neointima (genetics)
• Phosphorylation (genetics)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (genetics)
• Up-Regulation