叶酸通过下调ERK1/2信号通路抑制血管平滑肌细胞增殖和迁移

摘要

AIM: To elucidate the effect of folic acid (FA) on the proliferation and migration of vascular smooth muscle cells (VSMCs) and the related mechanism.METHODS:VSMCs were derived from SD rats and cultured in vitro.The cells were randomly divided and treated as indicated .CCK-8 assay and EdU cell proliferation assay were em-ployed to assess the viability and proliferation ability of the VSMCs .Wound healing assay and Transwell chamber assay were used to assess migration ability of the VSMCs .The protein level of proliferating cell nuclear antigen ( PCNA) , and the phosphorylation of platelet-derived growth factor receptor ( PDGFR) and extracellular signal-regulated kinase 1/2 ( ERK1/2 ) in the VSMCs were determined by Western blot .RESULTS:FA inhibited PDGF-induced VSMC viability and prolifera-tion in a dose-dependent manner ( P<0.05 ) .FA inhibited PDGF-induced VSMC migration in a dose-dependent manner (P<0.05).FA down-regulated PCNA and p-PDGFR protein levels and blocked PDGF-activated ERK1/2 signaling path-way.CONCLUSION:FA inhibits VSMC proliferation and migration via down-regulating the expression of PCNA and the level of p-PDGFR, and blocking ERK1/2 signal transduction pathway .%目的:探讨叶酸(folic acid,FA)对血管平滑肌细胞(VSMCs)增殖和迁移的影响及其机制.方法:取SD大鼠的主动脉,采用组织贴块法培养VSMCs,随机分组进行实验.采用CCK-8和EdU法检测叶酸对VSMCs活力和增殖能力的影响.采用划痕实验和Transwell法检测叶酸对VSMCs迁移和侵袭的影响.采用Western blot法检测细胞增殖核抗原(PCNA)蛋白表达以及血小板源性生长因子受体(PDGFR)和细胞外信号调节激酶1/2(ERK1/2)蛋白的磷酸化水平.结果:叶酸抑制血小板源性生长因子(PDGF)诱导的VSMCs的活力,并呈浓度依赖性(P<0.05).叶酸抑制PDGF诱导的VSMCs的迁移,并呈浓度依赖性(P<0.05).叶酸降低PCNA表达和PDG-FR磷酸化水平,并抑制PDGF激活的ERK1/2信号通路.结论:叶酸降低PDGF诱导的VSMCs PCNA和p-PDGFR蛋白水平,下调ERK1/2信号通路,从而抑制VSMCs的增殖和迁移.