| First Author | Zhou C | Year | 2023 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1870 |
| Issue | 1 | Pages | 166870 |
| PubMed ID | 37696161 | Mgi Jnum | J:341197 |
| Mgi Id | MGI:7532281 | Doi | 10.1016/j.bbadis.2023.166870 |
| Citation | Zhou C, et al. (2023) Fibroblast growth factor 21 ameliorates cholestatic liver injury via a hepatic FGFR4-JNK pathway. Biochim Biophys Acta Mol Basis Dis 1870(1):166870 |
| abstractText | Cholestasis is characterized by hepatic accumulation of cytotoxic bile acids (BAs), which often subsequently leads to liver injury, inflammation, fibrosis, and liver cirrhosis. Fibroblast growth factor 21 (FGF21) is a liver-secreted hormone with pleiotropic effects on the homeostasis of glucose, lipid, and energy metabolism. However, whether hepatic FGF21 plays a role in cholestatic liver injury remains elusive. We found that serum and hepatic FGF21 levels were significantly increased in response to cholestatic liver injury. Hepatocyte-specific deletion of Fgf21 exacerbated hepatic accumulation of BAs, further accentuating liver injury. Consistently, administration of rFGF21 ameliorated cholestatic liver injury caused by alpha-naphthylisothiocyanate (ANIT) treatment and Mdr2 deficiency. Mechanically, FGF21 activated a hepatic FGFR4-JNK signaling pathway to decrease Cyp7a1 expression, thereby reducing hepatic BAs pool. Our study demonstrates that hepatic FGF21 functions as an adaptive stress-responsive signal to downregulate BA biosynthesis, thereby ameliorating cholestatic liver injury, and FGF21 analogs may represent a candidate therapy for cholestatic liver diseases. |
