法尼酯X受体上调肝细胞中成纤维细胞生长因子21的表达

Farnesoid X receptor upregulates fibroblast growth factor 21 expression in cultured liver cells

目的研究法尼酯X受体(farnesoid X receptor,FXR)对成纤维细胞生长因子21(fibroblast growth factor,FGF21)表达的影响。方法用FXR特异性激动剂终浓度为0、50、100μmol/L的CDCA和0、1、5μmol/L的GW4064分别处理人肝癌细胞株HepG2和人胚胎肝细胞L02细胞后,用逆转录-聚合酶链法(RT-PCR)检测FXR特异性靶基因小异源二聚体配体(small heterodimer parterner,SHP)和FGF21 mRNA的表达变化,再用Western blot法检测FGF21蛋白表达水平的变化。结果用FXR特异性激动剂CDCA和GW4064刺激后,分别比较HepG2和L02细胞SHP与β-actin mRNART-PCR产物光密度比值,比值均明显增高(P<0.05),反应HepG2和L02细胞内SHP mRNA水平均明显升高,表明FXR在2种细胞中被激活;分别比较HepG2和L02细胞FGF21与β-actin RT-PCR产物光密度比值以及FGF21与β-actin蛋白光密度比值,比值均明显升高(P<0.05),表明FGF21 mRNA和蛋白水平均明显升高。结论激活的FXR可以上调FGF21的表达。

Objective To determine the effect of farnesoid X receptor（FXR） on the expression of fibroblast growth factor21（FGF21） in human hepatoblastoma HepG2 cells and hepatocyte L02 cells.Methods After HepG2 cells and L02 cells were treated with FXR agonist chenodesoxycholic acid（CDCA） at 0,50 or 100 μmol/L,or with another agonist GW4064 at 0,1 or 5 μmol/L respectively.The FXR specific target gene small heterodimer partner（SHP） and the FGF21 mRNA level were detected by reverse transcription-polymerase chain reaction（RT-PCR）,and FGF21 protein level was determined by Western blotting.Results After treated with CDCA and GW4064,the mRNA expression of SHP was significantly increased in the treated HepG2 and L02 cells when compared with the untreated cells respectively（P0.05）,which suggested that FXR was functionally activated in those cells.The mRNA and protein expressions of FGF21 were also increased in those treated cells（P0.05）.Conclusion FXR receptor upregulates the expression of FGF21 in hepatocytes.