Semaphorin 7A promotes human vascular smooth muscle cell proliferation and migration through theβ-catenin signaling pathway

查看全文 作　　者：XIAOSU [1]SONG;FEN [1]GAO;HONG [1]LI;WEIWEI [1]QIN;CHANJUAN [1]CHAI;GUOJUAN [1]SHI;HUIYU [1]YANG 机构地区：[1]Department of Cardiology,The Second Hospital of Shanxi Medical University,Taiyuan,030001,China 出　　处：《BIOCELL》索引2023年第47卷第4期,共10页 基　　金：supported by the Basic Research Program of Shanxi Province(Free Exploration)of China(20210302124416);Science and Technology Grant for Selected Returned Chinese Scholars of Shanxi Province of China(20220043);Four“Batches”Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province of China(2022XM08). 摘　　要：Background:Vascular smooth muscle cells(VSMCs)undergo a conversion from a contractile phenotype to a proliferative synthetic phenotype,contributing to the pathogenesis of cardiovascular diseases.Semaphorin 7A(SEMA7A)is a glycosylphosphatidylinositol-anchored membrane protein that plays an important role in vascular homeostasis by regulating endothelial cell behaviors.However,the expression and role of SEMA7A in VSMCs remain unclear.Methods:In this study,we screened for VSMC-regulating genes in publicly available datasets and analyzed the expression of SEMA7A in human coronary artery smooth muscle cells(hCASMCs)treated with platelet-derived growth factor-BB(PDGF-BB).The effects of SEMA7A overexpression and knockdown on hCASMC proliferation and migration were examined.The signaling pathways involved in the action of SEMA7A in hCASMCs were determined.Results:Bioinformatic analysis showed that SEMA7A was significantly dysregulated in VSMCs treated with oxidized low-density lipoprotein or overexpressing progerin,a pro-atherogenic gene.The PDGF-BB stimulation led to a concentration-and time-dependent induction of SEMA7A.Depletion of SEMA7A attenuated PDGF-BB-induced hCASMC proliferation and migration.Conversely,overexpression of SEMA7A enhanced hCASMC proliferation and migration.Mechanistically,SEMA7A stimulated the activation of theβ-catenin pathway and upregulated c-Myc,CCND1,and MMP7.Knockdown ofβ-catenin impaired SEMA7A-induced hCASMC proliferation and migration.Conclusions:SEMA7A triggers phenotype switching in VSMCs through theβ-catenin signaling pathway and may serve as a potential therapeutic target for cardiovascular diseases. 关 键 词：SEMA7A Vascular smooth muscle cell Phenotype switching REMODELING Β-CATENIN