STAT4 pathway activates homocysteine-induced proliferation, migration and senescence of human aorta smooth muscle cells / 中华普通外科杂志

ABSTRACT

Objective To investigate the role and mechanism of signal transducer and activator of transcription 4 (STAT4) in homocysteine (Hcy)-induced proliferation,migration and senescence of human aorta smooth muscle cells (VSMCs).Methods After VSMCs were incubated with Hcy (0-0.50 mmol/L) for various time periods,a CCK-8 assay was performed to determine proliferation activity.Modified Boyden chamber system (Transwell apparatus) was used to examine migration ability.A SA-β-gal staining kit was used to determine senescence status.Western blotting was performed to examine the expressions of STAT4 and phosphorylated STAT4 (p-STAT4) proteins,and ELISA was performed to examine MCP-1 expression.Results Hcy (from 0.05 mmol/L) significantly increased the proliferation of VSMCs (P ＜ 0.05).Hcy (from 0.10 mmol/L) significantly increased the migration of VSMCs (P ＜ 0.05).Hcy promoted the senescence of VSMC in a concentration-dependent manner,and significantly increased VSMC senescence when the concentration of Hcy reached 0.10 mmol/L (P ＜ 0.05).Hcy (from 0.10 mmol/L) treatment significantly increased the expression of p-STAT4 (P ＜ 0.05) and MCP-1 (P ＜ 0.05).Conclusions Hcy increases the proliferation,migration and senescence of VSMCs,probably by the activation of STAT4 pathway.