SUMO-1在ApoE-/-小鼠PM2.5暴露中调控血管HIF-1α/VEGF信号通路的研究

HIF-1/VEGF signal pathway regulated by SUMO-1 in vessel after ApoE-/- mice exposed to PM2.5

  • 摘要: 本文研究了ApoE-/-小鼠经PM2.5暴露后,其主动脉弓中SUMO-1、HIF-1及其靶基因血管内皮生长因子(VEGF)表达变化规律及HIF-1的SUMO化修饰情况。利用气管滴注方法将颗粒物滴入ApoE-/-小鼠,利用Western blot、QPCR检测小鼠主动脉中SUMO-1、HIF-1、VEGF的表达情况和CO-IP法检测SUMO-1及HIF-1共修饰情况。 结果显示: PM2.5暴露后,小鼠主动脉SUMO-1、HIF-1、VEGF的表达上调。CO-IP 显示:对照组SUMO-1没有对HIF-1α发生SUMO化修饰,PM2.5暴露后SUMO-1对HIF-1α产生了明显的SUMO化修饰。SUMO化的HIF-1与HIF-1α、HIF-1、VEGF蛋白均呈正相关。 PM2.5暴露可能通过上调细胞中SUMO-1的表达,稳定HIF-1α或者上调HIF-1的表达,进而影响VEGF的表达。

     

    Abstract: To evaluate the role of SUMO-1 in regulating HIF-1 and VEGF after ApoE-/- mice exposed to PM2.5. We investigated SUMOylation of HIF-1 by SUMO-1, and the expression patterns of SUMO-1, HIF-1, and vascular endothelial growth factor (VEGF), a well-characterized target gene of HIF-1, as well as their relationship to each other in aortic arch of mice. ApoE-/- mice was instilled with PM2.5 at dose of 8 mg/kg body weight by intratracheal instillation method. The transcription and expression of SUMO-1 and HIF-1 were detected respectively by QPCR,Western blot. Co-modification of SUMO-1and HIF-1 was determined by CO-IP. After PM2.5 exposure, expression of SUMO-1, HIF-1, VEGF in mouse aorta was up-regulated greatly. CO-IP displayed that SUMO modification of HIF-1 alpha didn’t appeared in control group, while HIF-1 alpha was modified by SUMO-1 after PM2.5 exposure. This work provides PM2.5 exposure may up-regulated expression of SUMO-1, then it stabilized or up-regulated the expression of HIF-1 alpha, enhance the transcriptional activity of HIF-1, and then influence the expression of VEGF.

     

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