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Am J Physiol Cell Physiol. 2016 Nov 1;311(5):C758-C767. doi: 10.1152/ajpcell.00033.2016. Epub 2016 Sep 14.

SM22α inhibits lamellipodium formation and migration via Ras-Arp2/3 signaling in synthetic VSMCs.

Author information

1
Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
2
Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China hanmei@hebmu.edu.cn.

Abstract

We previously demonstrated that smooth muscle (SM) 22α promotes the migration activity in contractile vascular smooth muscle cells (VSMCs). Based on the varied functions exhibited by SM22α in different VSMC phenotypes, we investigated the effect of SM22α on VSMC migration under pathological conditions. The results demonstrated that SM22α overexpression in synthetic VSMCs inhibited platelet-derived growth factor (PDGF)-BB-induced cell lamellipodium formation and migration, which was different from its action in contractile cells. The results indicated two distinct mechanisms underlying inhibition of lamellipodium formation by SM22α, increased actin dynamic stability and decreased Ras activity via interference with interactions between Ras and guanine nucleotide exchange factor. The former inhibited actin cytoskeleton rearrangement in the cell cortex, while the latter significantly disrupted actin nucleation activation of the Arp2/3 complex. Baicalin, a herb-derived flavonoid compound, inhibited VSMC migration via upregulation of SM22α expression in vitro and in vivo. These data suggest that SM22α regulates lamellipodium formation and cell migration in a phenotype-dependent manner in VSMCs, which may be a new therapeutic target for vascular lesion formation.

KEYWORDS:

Arp2/3; SM22α; cortex actin dynamics; phenotype; vascular smooth muscle cells

PMID:
27629412
DOI:
10.1152/ajpcell.00033.2016
[Indexed for MEDLINE]
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