Department of Molecular Biology, Pusan National University, Busan, 46241, Republic of Korea.
Advanced Molecular Research Centre, Department of Medical Research, Republic of Union of Myanmar, Yangon, 11191, Myanmar.
J Microbiol. 2023 Jul;61(7):693-702. doi: 10.1007/s12275-023-00065-1. Epub 2023 Aug 30.
Fibroblast growth factor 11 (FGF11) is a member of the intracellular FGF family, which shows different signal transmission compared with other FGF superfamily members. The molecular function of FGF11 is not clearly understood. In this study, we identified the inhibitory effect of FGF11 on hepatitis B virus (HBV) gene expression through transcriptional suppression. FGF11 decreased the mRNA and protein expression of HBV genes in liver cells. While the nuclear receptor FXRα1 increased HBV promoter transactivation, FGF11 decreased the FXRα-mediated gene induction of the HBV promoter by the FXRα agonist. Reduced endogenous levels of FXRα by siRNA and the dominant negative mutant protein (aa 1-187 without ligand binding domain) of FXRα expression indicated that HBV gene suppression by FGF11 is dependent on FXRα inhibition. In addition, FGF11 interacts with FXRα protein and reduces FXRα protein stability. These results indicate that FGF11 inhibits HBV replicative expression through the liver cell-specific transcription factor, FXRα, and suppresses HBV promoter activity. Our findings may contribute to the establishment of better regimens for the treatment of chronic HBV infections by including FGF11 to alter the bile acid mediated FXR pathway.
成纤维细胞生长因子 11（FGF11）是细胞内 FGF 家族的成员，与其他 FGF 超家族成员相比，它显示出不同的信号转导。FGF11 的分子功能尚不清楚。在这项研究中，我们通过转录抑制鉴定了 FGF11 对乙型肝炎病毒（HBV）基因表达的抑制作用。FGF11 降低了肝细胞中 HBV 基因的 mRNA 和蛋白表达。虽然核受体 FXRα1 增加了 HBV 启动子的转录激活，但 FGF11 降低了 FXRα 激动剂对 HBV 启动子的 FXRα 介导的基因诱导。通过 siRNA 降低内源性 FXRα 水平和 FXRα 表达的显性负突变蛋白（无配体结合域的 aa1-187）表明，FGF11 对 HBV 基因的抑制依赖于 FXRα 的抑制。此外，FGF11 与 FXRα 蛋白相互作用并降低 FXRα 蛋白稳定性。这些结果表明，FGF11 通过肝特异性转录因子 FXRα 抑制 HBV 复制性表达，并抑制 HBV 启动子活性。我们的发现可能有助于通过包括 FGF11 在内的更好的治疗方案来改变胆汁酸介导的 FXR 途径，从而治疗慢性 HBV 感染。
