title: SM22α inhibits lamellipodium formation and migration via Ras-Arp2/3 signaling in synthetic VSMCs.
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.
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Lv
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Yin
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Yu-Can
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Xie
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Dong
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Shu
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Biotechnology of Hebei Province, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Gui-Xia
authors.initials: GX
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Mei
authors.initials: M
authors.lastname: Han
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D003598:Cytoskeletal Proteins; D020662:Guanine Nucleotide Exchange Factors; D008840:Microfilament Proteins; D009124:Muscle Proteins; D010982:Platelet-Derived Growth Factor; C051615:transgelin; D018631:ras Proteins
keywords: Arp2/3; SM22α; cortex actin dynamics; phenotype; vascular smooth muscle cells