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  • 高熠辉,牟丽莎,崔婷婷,等.HSF4b基因敲除下调αB-晶状体蛋白表达介导白内障发生[J].同济大学学报(医学版),2021,42(5):597-603.    [点击复制]
  • GAO Yi-hui,MOU Li-sha,CUI Ting-ting,et al.Knockdown of HSF4b leads to cataract development through down-regulation of αB-crystallin expression[J].同济大学学报(医学版),2021,42(5):597-603.   [点击复制]
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HSF4b基因敲除下调αB-晶状体蛋白表达介导白内障发生
高熠辉,牟丽莎,崔婷婷,闫欣,徐晶莹,徐国彤
0
(同济大学医学院,上海200092;深圳大学第一附属医院转化医学研究院,广东 深圳518035)
摘要:
目的阐明热休克转录因子4b(HSF4b)对αB-晶状体蛋白(αB-crystallin, CRYAB)的调控在白内障发病过程中的作用及其机制。方法采用qPCR、Western印迹法和免疫荧光检测Hsf4tm1Xyk基因敲除小鼠晶状体中CRYAB和HSF4的表达情况;通过凝胶迁移实验、染色质免疫共沉淀、双报告基因检测等方法研究HSF4b对CRYAB的调控作用;通过免疫荧光分析和免疫共沉淀研究CRYAB与波形蛋白(vimentin, VIM)的相互作用。结果Hsf4tm1Xyk基因敲除小鼠晶状体中CRYAB表达下调;体外试验证实HSF4b和CRYAB的表达呈现正相关性;HSF4b直接与CRYAB启动子结合,激活CRYAB表达的转录过程;CRYAB与VIM存在相互作用。结论阐明了Hsf4tm1Xyk基因敲除小鼠中晶状体发育异常和白内障形成的分子机制。鉴定出CRYAB是HSF4b的下游调控分子。CRYAB对VIM具有稳定作用,有可能是抗白内障药物的作用靶点。
关键词:  晶状体疾病  白内障  热休克转录因子4b  αB-晶状体蛋白  波形蛋白
DOI:10.12289/j.issn.1008-0392.21148
投稿时间:2021-03-24
基金项目:上海市科学技术委员会科研计划项目(18411953400)
Knockdown of HSF4b leads to cataract development through down-regulation of αB-crystallin expression
GAO Yi-hui,MOU Li-sha,CUI Ting-ting,YAN Xin,XU Jing-ying,XU Guo-tong
(School of Medicine, Tongji University, Shanghai 200092, China;Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong Province, China)
Abstract:
ObjectiveTo investigate the effect of HSF4b on expression of αB-crystallin(CRYAB) and the development of cataract. MethodsQuantitative real-time polymerase chain reaction(qPCR), Western blot and immunofluorescence were used to detect the expression of αB-crystallin and HSF4 in the lens of Hsf4tm1Xyk-knockout mice. The regulative effects of HSF4b on αB-crystallin were examined by electrophoretic mobility shift assay, chromatin immunoprecipitation assay, and luciferase activity analysis. The interaction between αB-crystallin and vimentin(VIM) was studied by co-immunopre-cipitation and immunofluorescence. ResultsThe expression of αB-crystallin was down-regulated in the lens of Hsf4tm1Xyk-knockout mice. When HSF4b overexpressed or slienced in SRA01/04 cells, the expression of αB-crystallin showed in similar tendency at both mRNA level and protein level. HSF4b was directly bound to the HSE in αB-crystallin promoter and activated the expression of αB-crystallin. Meanwhile, αB-crystallin was able to interact with vimentin. ConclusionOur result shows that αB-crystallin may be a novel downstream molecular of HSF4b. The interaction of αB-crystallin and vimentin may be a key mechanism of cataract in Hsf4tm1Xyk knockout mice. Based on αB-crystallin and vimentin interaction, it is possible to find a novel therapeutic target for anti-cataract drugs.
Key words:  lens diseases  cataract  HSF4b  αB-crystallin  vimentin

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