High glucose induces vascular smooth muscle cell proliferation and migration through activation of Src/Stat3 signaling pathway
10.3969/j.issn.1000-4718.2017.07.014
- VernacularTitle: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
- Author:
Jun WANG
;
Yihui QIN
- Keywords:
Src tyrosine kinase;
Signal transducer and activator of transcription 3;
High glucose;
Vascular smooth muscle cells;
Cells proliferation;
Cells migration
- From:
Chinese Journal of Pathophysiology
2017;33(7):1237-1243
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the role of Src tyrosine kinase (Src)/signal transducer and activator of transcription 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 detected 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 further confirm the role of Src in HG-induced VSMC proliferation, the VSMCs were exposed to HG (40 mmol/L) and co-treated 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.
