PDGF-BB下调血管平滑肌标志物SM22α表达的机制

血管平滑肌细胞（vascular smooth muscle cell,VSMC）表型转化是血管重塑性疾病的细胞病理学基础,血小板源性生长因子（platelet-derived growth factor,PDGF）-BB抑制平滑肌分化标志基因表达、加速其降解,是VSMC表型转化的关键。该研究用PDGF-BB刺激VSMC诱导细胞发生表型转化,利用Western blot和免疫共沉淀等技术,检测PDGF-BB对早期分化相关基因平滑肌22 alpha（smooth muscle 22 alpha,SM22α）磷酸化与泛素化的影响。实验结果显示,PDGF-BB促进VSMC增殖;上调增殖相关蛋白PCNA的表达,下调分化相关蛋白SM22α与SMα-actin的表达;诱导SM22α发生磷酸化和泛素化,而且,该过程与SM22α水平下调具有时相相关性;抑制剂阻断分析证实,ERK和PKC参与介导了PDGF-BB诱导的SM22α磷酸化。以上结果提示,在VSMCs表型转化中,PDGF-BB可能是通过激活ERK-PKC信号通路,促进SM22α的磷酸化和泛素依赖的蛋白质降解。

Mechanism of PDGF-BB Down-regulating SM22a Expression in Vascular Smooth Muscle Cells

Vascular smooth muscle cell （VSMC） phenotypic modulation is considered to be key event in the development of vascular proliferative disorders. Platelet-derived growth factor （PDGF）-BB inhibits the expression of differentiation marker genes and promotes their degradation. Here, the phosphorylation and ubiquitination of smooth muscle 22 alpha （SM22a） stimulated by PDGF-BB was identified by Western blot analysis and coimmu- noprecipitation analysis. The results showed PDGF-BB induced the proliferation of VSMCs. PDGF-BB increased the expression of PCNA, and reduced the levels of SM α-actin and SM22α. PDGF-BB increased the expression of phosphorylated and ubiquitinated SM22α, and the raise of phosphorylated level was earlier than the effect to ubiquitination. Moreover, after the ERK and PKC activity were inhibited, the SM22α phosphorylation and destabilization stimulating by PDGF-BB was disappeared. Collectively, these results indicate that destabilization of SM22α following PDGF-BB is mediated, at least in part, through ERK-PKC-depended pathway.