Src/Stat3通路在高糖诱导的血管平滑肌细胞增殖及迁移中的作用  

High glucose induces vascular smooth muscle cell proliferation and migration through activation of Src/Stat3 signaling pathway

作　　者：王军[1] 秦逸辉[1] 

机构地区：[1]厦门大学附属成功医院(解放军第174医院)老年病科,福建厦门361003

出　　处：《中国病理生理杂志》2017年第7期1237-1243,共7页Chinese Journal of Pathophysiology

基　　金：南京军区医药卫生科研基金(No.11MA073)

摘　　要：目的:探讨Src酪氨酸激酶(Src)/信号转导子和转录激活子3(Stat3)在高糖(HG)诱导的血管平滑肌细胞(VSMCs)增殖和迁移中的作用。方法:首先将VSMC细胞株A7R5与HG(10~40 mmol/L)共同孵育24h,MTT法及EdU染色检测VSMCs增殖,Transwell小室检测VSMCs迁移,Western blot检测p-Src、Src、p-Stat3和Stat3的蛋白水平。q PCR检测Stat3靶基因细胞周期蛋白D1(cyclin D1)、Myc、基质金属蛋白酶2(MMP2)及基质金属蛋白酶9(MMP9)的表达。为了进一步证实Src在高糖诱导VSMCs增殖和迁移中的作用,将HG与Src抑制剂saracatinib(100 nmol/L)共同孵育24 h,观察Src对HG诱导VSMCs增殖、迁移及Stat3激活的影响。结果:HG能浓度依赖性地促进VSMCs的增殖及迁移并激活Src和Stat3,上调Stat3靶基因cyclin D1、Myc、MMP2及MMP9的表达。抑制Src激活可抑制HG诱导的VSMCs增殖及Stat3的激活,同时下调cyclin D1及Myc的表达。结论:Src/Stat3通路可能在HG诱导的VSMCs增殖及迁移中发挥重要作用。AIM ： To investigate the role of Src tyrosine kinase （ Src ） /signal transducer and activator of tran-scription 3 （Stat3） signaling pathway in high glucose （HG）-induced vascular smooth muscle cell （ VSMC） proliferation and migration. METHODS： VSMCs were incubated with HG （10 ？40 mmol/L） for 24 h. The cell proliferation was de-tected by MTT assay and EdU staining, while the migration ability of VSMCs was measured by Transwell assay. The protein levels of p-Src, Src, p-Stat3, Stat3 and GAPDH were determined by Western blot. The mRNA expression levels of cyclin D1, Myc, matrix metalloproteinase 2 （ MMP2） and matrix metalloproteinase 9 （ MMP9） were detected by qPCR. To fur-ther confirm the role of Src in HG-induced VSMC proliferation, the VSMCs were exposed to HG （40 mmol/L） and co-trea-ted with Src inhibitor saracatinib （100 nmol/L） for 24 h, and then the proliferation ability and the Stat3 activity of the cells were analyzed. RESULTS： Treatment with HG dose-dependently enhanced the cell viability, increased the ratio of EdU- positive cells, and raised the migration cell number, the protein levels of p-Src and p-Stat3 and the mRNA levels of cyclin D1, Myc, MMP2 and MMP9. Inhibition of Src inhibited HG-induced VSMC proliferation and migration, and suppressed Stat3 activation and the expression of Stat3 target genes cyclin D1 , Myc, MMP2 and MMP9. CONCLUSION： Src/Stat3 signaling pathway might play an important role in HG-induced VSMC proliferation and migration.

关 键 词：SRC酪氨酸激酶 信号转导子和转录激活子3 高糖 血管平滑肌 细胞增殖 细胞迁移 

分 类 号：R587.1[医药卫生—内分泌] R363.2[医药卫生—内科学]