低氧/低氧诱导因子-1α通过TGF-β1诱导人肝内胆管上皮细胞上皮间质转化  

The mechanism of epithelial-mesenchymal transition of human intrahepatic biliary epithelial cells induced by hypoxia/hypoxic inducible factor-1αthrough tgf-β1

作　　者：杨再兴[1] 梁艳[2] 刘东红[1] 张振成 罗婉婉 毛盼璎 YANG Zaixing;LIANG Yan;LIU Donghong;ZHANG Zhencheng;LUO Wanwan;MAO Panying(Department of Laboratory Medicine,Taizhou First People’s Hospital,Taizhou 318020,China;Department of Laboratory Diagnostics,Shanghai Changzheng Hospital,Shanghai 200003,China)

机构地区：[1]台州市第一人民医院检验科,浙江台州318020 [2]上海长征医院实验诊断科,上海200003

出　　处：《温州医科大学学报》2021年第1期40-44,共5页Journal of Wenzhou Medical University

基　　金：浙江省医药卫生科技计划项目(2019KY241,2020KY1040)。

摘　　要：目的:探讨低氧/低氧诱导因子-1α(HIF-1α)对人肝内胆管上皮细胞(HIBEC)上皮-间质转化(EMT)的诱导作用及其分子机制。方法:HIBEC在1%氧浓度的低氧环境中培养,分析细胞迁移、侵袭能力的变化,以及EMT相关标志E-钙黏蛋白和S100A4的表达水平。以HIF-1α的siRNA和转化生长因子-β1(TGF-β1)抑制剂LY364947分别沉默或抑制HIF-1α和TGF-β1,再重复上述实验。结果:与常氧培养相比较,低氧条件下,HIBEC的细胞迁移和侵袭能力明显增强,上皮细胞标志物E-钙黏蛋白表达明显下降,间质细胞标志物S100A4表达明显升高(P<0.05)。以HIF-1α的siRNA和TGF-β1分别沉默或抑制HIF-1α和TGF-β1后,上述低氧引起的HIBEC生物学变化均受到明显抑制(P<0.05)。结论:低氧可以通过活化HIF-1α诱导HIBEC发生EMT,这种诱导作用主要是通过TGF-β1完成的。Objective:To investigate the role of hypoxia/hypoxic inducible factor-1α(HIF-1α)in inducing epithelial-mesenchymal transition of human intrahepatic biliary epithelial cells(HIBEC)as well as its molecular mechanisms.Methods:Under the condition of hypoxia(1%O2),HIBECs were cultured in vitro and analyzed for mobility,invasiveness and expression levels of EMT-related markers including E-cadherin and S100A4.The above-mentioned experiments were repeated with HIF-1αsilenced by siRNA and transforming growth factorβ1(TGF-β1)inhibited by inhibitor LY364947.Results:Under the condition of hypoxia,in contrast to normoxia,HIBECs showed markedly enhanced mobility and invasiveness as well as significant downregulation of E-cadherin and upregulation of S100A4.After HIF-1αsilence or TGF-β1 inhibition,above-mentioned biological changes of HIBECs were significantly inhibited under hypoxia.Conclusion:Hypoxia can induce EMT of HIBECs by activating HIF-1α.TGF-β1 plays an important role in hypoxia/HIF-1α-induced EMT of HIBECs.

关 键 词：低氧 低氧诱导因子-1Α 转化生长因子-Β1 肝内胆管上皮细胞 上皮间质转化 

分 类 号：R363.2[医药卫生—病理学]