De-hui Qian1, Pan Gao2, Huan Feng3, Zhe-Xue Qin1, Jia-bei Li1, Lan Huang4. 1. Department of Cardiology, Second hospital affiliated to Third military medical university, XinQiao Hospital, ChongQing, 400037, China. 2. Department of Geriatrics, First hospital affiliated to Third military medical university, Southwest Hospital, ChongQing, 400038, China. 3. Division of Nursing, Second hospital affiliated to Third military medical university, XinQiao Hospital, ChongQing, 400037, China. 4. Department of Cardiology, Second hospital affiliated to Third military medical university, XinQiao Hospital, ChongQing, 400037, China. Electronic address: Huanglan260@126.com.
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.
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 ratballoon 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: Yu Zhao; Yunfei Li; Ling Tong; Xinying Liang; Han Zhang; Lan Li; Guanwei Fan; Yi Wang Journal: Front Physiol Date: 2018-02-06 Impact factor: 4.566
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