Fibroblast growth factor 15 deficiency impairs liver regeneration in mice

Published

Journal Article

Fibroblast growth factor (FGF) 15 (human homolog, FGF19) is an endocrine FGF highly expressed in the small intestine of mice. Emerging evidence suggests that FGF15 is critical for regulating hepatic functions; however, the role of FGF15 in liver regeneration is unclear. This study assessed whether liver regeneration is altered in FGF15 knockout (KO) mice following 2/3 partial hepatectomy (PHx). The results showed that FGF15 KO mice had marked mortality, with the survival rate influenced by genetic background. Compared with wild-type mice, the KO mice displayed extensive liver necrosis and marked elevation of serum bile acids and bilirubin. Furthermore, hepatocyte proliferation was reduced in the KO mice because of impaired cell cycle progression. After PHx, the KO mice had weaker activation of signaling pathways that are important for liver regeneration, including signal transducer and activator of transcription 3, nuclear factor-κB, and mitogen-activated protein kinase. Examination of the KO mice at early time points after PHx revealed a reduced and/or delayed induction of immediate-early response genes, including growth-control transcription factors that are critical for liver regeneration. In conclusion, the results suggest that FGF15 deficiency severely impairs liver regeneration in mice after PHx. The underlying mechanism is likely the result of disrupted bile acid homeostasis and impaired priming of hepatocyte proliferation.

Full Text

Duke Authors

Cited Authors

  • Kong, B; Huang, J; Zhu, Y; Li, G; Williams, J; Shen, S; Aleksunes, LM; Richardson, JR; Apte, U; Rudnick, DA; Guo, GL

Published Date

  • May 15, 2014

Published In

Volume / Issue

  • 306 / 10

Start / End Page

  • G893 - G902

Published By

Electronic International Standard Serial Number (EISSN)

  • 1522-1547

International Standard Serial Number (ISSN)

  • 0193-1857

Digital Object Identifier (DOI)

  • 10.1152/ajpgi.00337.2013

Language

  • en