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Fibroblast growth factor 15 deficiency impairs liver regeneration in mice

Publication ,  Journal Article
Kong, B; Huang, J; Zhu, Y; Li, G; Williams, J; Shen, S; Aleksunes, LM; Richardson, JR; Apte, U; Rudnick, DA; Guo, GL
Published in: American Journal of Physiology-Gastrointestinal and Liver Physiology
May 15, 2014

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.

Duke Scholars

Published In

American Journal of Physiology-Gastrointestinal and Liver Physiology

DOI

EISSN

1522-1547

ISSN

0193-1857

Publication Date

May 15, 2014

Volume

306

Issue

10

Start / End Page

G893 / G902

Publisher

American Physiological Society

Related Subject Headings

  • Gastroenterology & Hepatology
  • 1116 Medical Physiology
  • 0606 Physiology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kong, B., Huang, J., Zhu, Y., Li, G., Williams, J., Shen, S., … Guo, G. L. (2014). Fibroblast growth factor 15 deficiency impairs liver regeneration in mice. American Journal of Physiology-Gastrointestinal and Liver Physiology, 306(10), G893–G902. https://doi.org/10.1152/ajpgi.00337.2013
Kong, Bo, Jiansheng Huang, Yan Zhu, Guodong Li, Jessica Williams, Steven Shen, Lauren M. Aleksunes, et al. “Fibroblast growth factor 15 deficiency impairs liver regeneration in mice.” American Journal of Physiology-Gastrointestinal and Liver Physiology 306, no. 10 (May 15, 2014): G893–902. https://doi.org/10.1152/ajpgi.00337.2013.
Kong B, Huang J, Zhu Y, Li G, Williams J, Shen S, et al. Fibroblast growth factor 15 deficiency impairs liver regeneration in mice. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2014 May 15;306(10):G893–902.
Kong, Bo, et al. “Fibroblast growth factor 15 deficiency impairs liver regeneration in mice.” American Journal of Physiology-Gastrointestinal and Liver Physiology, vol. 306, no. 10, American Physiological Society, May 2014, pp. G893–902. Crossref, doi:10.1152/ajpgi.00337.2013.
Kong B, Huang J, Zhu Y, Li G, Williams J, Shen S, Aleksunes LM, Richardson JR, Apte U, Rudnick DA, Guo GL. Fibroblast growth factor 15 deficiency impairs liver regeneration in mice. American Journal of Physiology-Gastrointestinal and Liver Physiology. American Physiological Society; 2014 May 15;306(10):G893–G902.

Published In

American Journal of Physiology-Gastrointestinal and Liver Physiology

DOI

EISSN

1522-1547

ISSN

0193-1857

Publication Date

May 15, 2014

Volume

306

Issue

10

Start / End Page

G893 / G902

Publisher

American Physiological Society

Related Subject Headings

  • Gastroenterology & Hepatology
  • 1116 Medical Physiology
  • 0606 Physiology