NF-κB激活gp96转录从而促进肝细胞生长、细胞周期进展和细胞转化  

NF-κB-induced gp96 up-regulation promotes hepatocyte growth,cell cycle progression and transition

作　　者：冯聪[1,2] 吴博[1,2] 范红霞[2] 李长菲[2] 孟颂东[2] 

机构地区：[1]安徽大学生命科学学院,安徽合肥230601 [2]中国科学院微生物研究所中国科学院病原微生物与免疫学重点实验室,北京100101

出　　处：《微生物学报》2014年第10期1212-1220,共9页Acta Microbiologica Sinica

基　　金：国家自然科学基金(31230026,81321063,81102018)~~

摘　　要：【目的】探讨乙肝感染中gp96上调的机制及其可能发挥的病理学机制。【方法】首先通过生物信息学、Real-time PCR、荧光报告基因和Western blot研究NF-κB激活gp96表达的机制。进一步通过在肝细胞中过表达或敲低gp96的水平,运用CCK-8法和流式检测分析gp96对肝细胞增殖、凋亡,和细胞周期的影响,通过检测肝细胞EMT发生和细胞集落形成实验,分析gp96对于HCC发生的作用。【结果】NF-κB与gp96启动子上NF-κB结合位点结合,激活gp96的表达。实验结果显示,gp96能够促进肝细胞增殖、抑制凋亡,促进细胞周期从静息期向分裂期的转化,同时促进肝细胞EMT发生和细胞集落的形成。【结论】NF-κB通过活化gp96启动子上调其表达,为HBV慢性感染上调gp96的机制提供了线索,同时提示gp96在慢性炎症引发HCC过程中发挥重要作用。[ Objective] To investigate the mechanism of gp96 raised during hepatitis B virus （HBV） infection and the pathological mechanism. [ Methods ] The mechanism of NF-KB activating gp96 expression was determined by bioinformatics analysis, luciferase reporter assay, real-time PCR and Western blot. The effect of over-expression and knockdown gp96 expression by transfection or RNA interference on hepatocyte proliferation, apoptosis and cell cycle was examined by CCK-8 and flow cytometry. The role of gp96 for HCC development was determined by epithelial-mesenehymal transition （EMT） and colony formation assay. [ Results] NF-kB significantly increased the gp96 expression by binding to the NF-kB binding site. Over-expression and knockdown studies both show that gp96 promoted hepatocyte proliferation, inhibited apoptosis, and induced GO/G1 to S phase cell cycle progression. Moreover, gp96 induced epithelial- mesenchymal transition and increased colony formation ability of hepatoeytes. [ Conclusion ] Our results therefore provide insights in chronic HBV infection-induced gp96 expression, and indicate that elevated gp96 may contribute to HCC development during chronic inflammation.

关 键 词：NF-KB GP96 细胞生长 细胞周期 EMT 

分 类 号：R363[医药卫生—病理学]