The ileal FGF15/19 to hepatic FGFR4 axis regulates liver regeneration after partial hepatectomy in mice

Journal of Physiology and Biochemistry
Qiang LiXiaoshun He

Abstract

Fibroblast growth factor (FGF) has been considered to modulate liver regeneration (LR) after partial hepatectomy (PH) at the tissue level. Previous studies have demonstrated that FGF15 and FGF19 induce the activation of its receptor, FGF receptor 4 (FGFR4), which can promote hepatocellular carcinoma progression and regulate liver lipid metabolism. In this study, we aimed to explore the role of the ileal FGF15/19- hepatic FGFR4 axis in the LR after PH. Male C57BL/6 mice aged 8-12 weeks were partially hepatectomized and assessed for expression of ileal FGF15/19 to hepatic FGFR4 signaling. We used recombinant human FGF19 protein and a small interfering RNA (siRNA) of FGFR4 to regulate expression of the FGF15/19-FGFR4 axis in vitro and in vivo. The proliferation and cell cycle of hepatocytes, the expression levels of FGF15/19-FGFR4 downstream molecules, liver recovery, and lipid metabolism were assessed. We found that both ileal and serum FGF15 expression were upregulated and hepatic FGFR4 was activated after PH in mice. FGF15/19 promoted cell cycle progression, enhanced proliferation, and reduced hepatic lipid accumulation of hepatocytes both in vitro and in vivo. Furthermore, the proliferative effect and lipid regulatory properti...Continue Reading

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Citations

Nov 10, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yuan TianAndrew D Patterson
Feb 8, 2020·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Cláudia Nunes OliveiraAldo Cunha Medeiros
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Jan 24, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Courtney M WilliamsChristopher Daly
Feb 12, 2021·Nature Reviews. Gastroenterology & Hepatology·Lulu SunFrank J Gonzalez
Oct 10, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Na YangYu-Bo Li

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Methods Mentioned

BETA
immunoprecipitation
electrophoresis
X-ray
pull down
flow cytometry
enzyme-linked immunosorbent assay
Assay
PCR

Software Mentioned

ImageJ1
ImageJ

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