Lv Pin, Zhang Fan, Yin Ya-Juan, Wang Yu-Can, Gao Min, Xie Xiao-Li, Zhao Li-Li, Dong Li-Hua, Lin Yan-Ling, Shu Ya-Nan, Zhang Dan-Dan, Liu Gui-Xia, Han Mei
Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China
Am J Physiol Cell Physiol. 2016 Nov 1;311(5):C758-C767. doi: 10.1152/ajpcell.00033.2016. Epub 2016 Sep 14.
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.
我们先前证明，平滑肌（SM）22α可促进收缩性血管平滑肌细胞（VSMC）的迁移活性。基于SM22α在不同VSMC表型中表现出的多种功能，我们研究了SM22α在病理条件下对VSMC迁移的影响。结果表明，合成型VSMC中SM22α的过表达抑制了血小板衍生生长因子（PDGF）-BB诱导的细胞板状伪足形成和迁移，这与其在收缩性细胞中的作用不同。结果表明，SM22α抑制板状伪足形成存在两种不同机制，即通过干扰Ras与鸟嘌呤核苷酸交换因子之间的相互作用增加肌动蛋白动态稳定性并降低Ras活性。前者抑制细胞皮质中的肌动蛋白细胞骨架重排，而后者则显著破坏Arp2/3复合物的肌动蛋白成核激活。黄芩苷是一种源自草药的黄酮类化合物，在体外和体内均通过上调SM22α表达来抑制VSMC迁移。这些数据表明，SM22α以表型依赖性方式调节VSMC中的板状伪足形成和细胞迁移，这可能是血管病变形成的一个新的治疗靶点。
