缺氧诱导因子1α抑制microRNA-92a调控上皮细胞间质化

The lower microRNA-92a regulated epithelial-mesenchymal transition with HIF-1α

【目的】探讨缺氧诱导因子1α(hypoxia inducible factor-1α,HIF-1α)通过抑制microRNA-92a(miR-92a)调控口腔黏膜上皮细胞间质化的机制。【方法】15只健康雌性Wistar大鼠分为常氧对照组、缺氧12 h组、缺氧24 h组。常氧对照组常氧饲养,后两组大鼠缺氧饲养,均放置于抽取到相当于海拔7 000 m的低压缺氧舱,分别持续缺氧12、24 h。3组大鼠麻醉处死后提取口腔黏膜上皮,HE染色观察上皮组织形态,qPCR测定miR-92a、HIF-1α、E-钙黏蛋白、波形蛋白基因表达水平,Western blotting测定其相应蛋白表达水平。【结果】缺氧12 h组、缺氧24 h组同常氧对照组相比,缺氧组钉突变短、基底膜增生,HIF-1αm RNA表达比分别为1.273、1.212,蛋白表达比分别为2.575、1.860;miR-92a表达比分别为0.238、0.465;E-钙黏蛋白mRNA表达比为0.774、0.702,蛋白表达比为0.768、0.773;波形蛋白mRNA表达比为1.253、1.307,蛋白表达比为2.722、3.476。【结论】缺氧条件下HIF-1α通过抑制miR-92a诱导口腔黏膜上皮间质化。

【Objective】To investigate the mechanism which the lower microRNA-92a(miR-92a)regulated oral mucosal epithelialmesenchymal transition with hypoxia inducible factor-1α(HIF-1α).【Methods】The subjects were divided into three groups:oxygen control,hypoxia 12 h,hypoxia 24 h.In oxygen control group,the rats live in oxygen cabin,but in hypoxia groups,the rats were lived in hypobaric hypoxia cabin where air extraction amount to altitude 7 000 m,12 h or 24 h.Then,the rats were sacrificed and the oral mucosal epithelial tissues were extracted and frozen.The tissue shapes with HE staining were observed under light microscope,the expression of miR-92a in epithelial tissue were detected by real-time quantitative polymerase chain reaction(qPCR),and the expression of HIF-1α,cadherin and vimentin was studied by qPCR and western blotting.【Results】Compared to epithelial tissues in normoxic control group,the tissues nails in hypoxia 12h and 24h group were shorten;the basement membrane in two hypoxia group was hyperplasia.The expression ratio of miR-92a in hypoxia 12h or 24h to the one in control group was 0.238 or 0.465.Similarly,the HIF-1αmRNA expression ratio was 1.273 or 1.212;the protein expression ratio was 2.575 or 1.860.The cadherin mRNA expression ratio was 0.774 or 0.702;the protein expression ratio was 0.768 or 0.773.The vimentin mRNA expression ratio was 1.253 or 1.307;the protein expression ratio was 2.722 or 3.476.【Conclusion】The lower miR-92a regulated oral mucosal epithelial-mesenchymal transition with HIF-1α.