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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。
Phenotypic transformation of vascular smooth muscle cells (VSMCs) is the cytopathological basis of vascular remodeling diseases. Platelet-derived growth factor (PDGF) -BB inhibits the expression of smooth muscle differentiation marker genes and accelerates Its degradation, is the key to VSMC phenotype transformation. In this study, VSMCs were induced by PDGF-BB to induce phenotypic transformation. Western blot and co-immunoprecipitation were used to detect the effects of PDGF-BB on phosphorylation of smooth muscle 22 alpha (SM22α) and ubiquitin The impact of change. The results showed that PDGF-BB promoted the proliferation of VSMC, up-regulated the expression of proliferating cell nuclear antigen-PCNA and down-regulated the expressions of SM22α and SMα-actin, and induced the phosphorylation and ubiquitination of SM22α. In addition, Inhibitory blockade analysis confirmed that ERK and PKC are involved in mediating PDGF-BB-induced SM22α phosphorylation. The above results suggest that PDGF-BB may promote SM22α phosphorylation and ubiquitin-dependent protein degradation by activating the ERK-PKC signaling pathway in VSMCs phenotypic transformation.