法尼酯X受体在增强胎肝细胞中对B类清道夫受体Ⅰ表达的研究

Research of FXR in increasing expression of SR-BI in hepatocyte

目的探讨法尼酯X受体(farnesoid X receptor,FXR)在肝细胞中对B类清道夫受体I(scavenger receptor class B type I,SR-BI)表达的影响及可能机制。方法用FXR的特异性激动剂GW4064刺激胚胎肝细胞L02,经RT-PCR检测FXR特异性靶基因SHP(small heterodimer partner)mRNA的表达;经RT-PCR、荧光实时定量PCR和Western blot检测SR-BI的表达;在线分析、预测SR-BI基因启动子区中FXR的可能结合位点;最后经RT-PCR检测FXR的靶基因PPARγ(过氧化物酶体增殖物激活受体γ)mRNA的表达。结果FXR的特异性配体GW4064作用于L02细胞后,SHP mRNA表达明显上调,表明FXR在L02细胞中具有功能活性。FXR活化后可在转录和翻译水平上调SR-BI的表达,同时上调PPARγ的表达。经在线分析,未在SR-BI启动子区域找到FXR的经典结合位点。结论FXR在肝细胞中可上调SR-BI的表达,其机制可能与上调PPARγ有关。

Objective To investigate the effect of farnesoid X receptor（FXR） on the expression of scavenger receptor class B type I and its potential mechanism. Methods Human hepatocyte L02 cells were treated with FXR specific agonist GW4064 and SHP （the specific target gene of FXR）mRNA was detected by RT-PCR SR-BI mRNA and protein were assayed by using RT-PCR, real time PCR and Western blot. The potential binding site of FXR in the SR-BI promoter region was on line analyzed. Finally,determining the level of PPARγ by RT-PCR. Results The level of SHP mRNA was increased, treated with FXR specific agonist GW4064 with different concentrations for 24h respectively in L02, which demonstrated FXR was functional in L02. SR-BI were raised in both mRNA and protein level after FXR activation. Meanwhile,the level of PPARγ mRNA was inclined by actived FXR. On line analyzing,the classical binding site of FXR in the promoter of SR-BI could not be found. Conclusion FXR could increase the expression of scavenger receptor class B type I in hepatocyte,which might be related to upregulation of PPARγ.