HSF1通过调节ATF6-XBP1通路影响肝脏AA淀粉样变性  

HSF1 affects hepatic AA amyloidosis by regulating ATF6-XBP1 pathway

作　　者：王琨璐 付志豪 王宇彬 刘元昊 高泽晗 冷建宁 尚晶 钱金泽[1] 刘巍[1] WANG Kun-lu;FU Zhi-hao;WANG Yu-bin;LIU Yuan-hao;GAO Ze-han;LENG Jian-ning;SHANG Jing;QIAN Jin-ze;LIU Wei(Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China)

机构地区：[1]河北医科大学病理学教研室,石家庄050017

出　　处：《临床与实验病理学杂志》2020年第11期1269-1273,共5页Chinese Journal of Clinical and Experimental Pathology

基　　金：河北省2018、2019年大学生创新性实验项目(USIP2018078、USIP2019217);河北省自然基金精准医学项目(H2020206399)。

摘　　要：目的探讨ATF6-XBP1通路在肝脏AA淀粉样变中的作用机制,以及HSF1对其通路的调节作用。方法使用HSF1基因敲除小鼠构建肝脏淀粉样变模型,以野生型为对照组。采集各组小鼠肝脏组织,通过刚果红和免疫组化SP法比较各组肝脏淀粉样变沉积程度,同时对ATF6和XBP1的mRNA及蛋白水平进行检测。结果刚果红染色和免疫组化SP法染色:敲除型实验组肝脏淀粉样物质沉积程度显著高于野生型实验组(P<0.01),敲除型空白组、野生型空白组肝脏未见淀粉样沉积。Western blot结果显示,敲除型实验组肝脏中GRP78蛋白表达量显著低于野生型实验组。RT-PCR结果显示:野生型实验组ATF6 mRNA表达略低于野生型空白组,前者的XBP1 mRNA表达则显著高于后者;而在敲除型组中ATF6、XBP1 mRNA表达呈相反趋势。结论HSF1通过调控ATF6-XBP1通路影响肝脏AA淀粉样变的形成与沉积,证实热休克反应与未折叠蛋白质反应的相互作用,为淀粉样变疾病的临床预防与治疗提供新的理论依据。Purpose To explore the mechanism of ATF6-XBP1 pathways in hepatic AA amyloidosis and the regulation of HSP1 pathways.Methods HSF1 knockout mice were used to construct a hepatic amyloidosis model,and the wild-type mice were used as the control group.The liver tissues of mice in each group were collected,and the degree of amyloidosis deposition in the liver was compared between groups by Congo red and immunohistochemical of SP methods at the same time,their mRNA and protein levels of ATF6 and XBP1 were detected.Results Congo red staining and immunohistochemical staining showed that the degree of amyloid deposition in the liver of the knockout experimental group was significantly higher than that of the wild-type experimental group(P<0.01),and there was no amyloid deposition in the liver of the other two blank groups.Western blot showed that compared to the wild-type experimental group,expression of GRP78 protein in the liver decreased significantly in the knockout experimental group.RT-PCR results showed the expression of ATF6 mRNA in the wild-type experimental group was slightly lower than that of in the wild-type blank group,but the expression of XBP1 mRNA in the former was significantly higher than that in the latter.However,the expression of ATF6 and XBP1 mRNA in the knockout group showed an opposite trends.Conclusion HSF1 affects the formation and deposition of hepatic AA amyloidosis by regulating ATF6-XBP1 pathway,and confirms the interaction between heat shock response and unfolded protein response which provided a new theoretical basis for the clinical prevention and treatment of amyloidosis.

关 键 词：肝脏肿瘤 AA淀粉样变性 HSF1 ATF6 XBP1 

分 类 号：R363.22[医药卫生—病理学]