Fibroblast Growth Factor 11 Inhibits Hepatitis B Virus Gene Expression Through FXRα Suppression

Area of Science:

• Molecular biology
• Hepatology
• Virology

Background:

• Fibroblast growth factor 11 (FGF11) is an intracellular FGF family member with poorly understood functions.
• Hepatitis B virus (HBV) infection remains a significant global health concern, necessitating novel therapeutic strategies.

Purpose of the Study:

• To investigate the role of FGF11 in regulating hepatitis B virus (HBV) gene expression.
• To elucidate the molecular mechanism underlying FGF11's effect on HBV replication.

Main Methods:

• Assessing the impact of FGF11 on HBV gene mRNA and protein levels in liver cells.
• Investigating the interaction between FGF11 and the nuclear receptor FXRα (farnesoid X receptor alpha).
• Utilizing siRNA and dominant-negative mutants to confirm FXRα's role in FGF11-mediated suppression.

Main Results:

• FGF11 significantly decreased HBV gene expression at both mRNA and protein levels.
• FGF11 inhibited FXRα-mediated transactivation of the HBV promoter.
• FGF11 was found to interact with FXRα, reducing its protein stability and confirming FXRα dependence for HBV suppression.
• FGF11 suppresses HBV replication by inhibiting the liver cell-specific transcription factor FXRα.

Conclusions:

• FGF11 exerts an inhibitory effect on HBV gene expression through transcriptional suppression mediated by FXRα.
• FGF11's interaction with FXRα and subsequent reduction in its stability are key mechanisms for inhibiting HBV replication.
• Targeting the FGF11-FXRα pathway presents a potential novel therapeutic approach for chronic HBV infections, possibly by modulating the bile acid-mediated FXR pathway.