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.
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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)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
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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
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