Direct and Indirect Effects of Fibroblast Growth Factor (FGF) 15 and FGF19 on Liver Fibrosis Development.

ABSTRACT: Farnesoid X receptor (FXR) induces fibroblast growth factor 15 (FGF15; human ortholog FGF19) in the gut to potently inhibit bile acid (BA) synthesis in the liver. FXR activation in hepatic stellate cells (HSCs) reduces liver fibrosis (LF). Fgf15^-/- mice develop attenuated LF, but the underlying mechanisms for this protection are unclear. We hypothesized that FGF15/19 functions as a profibrotic mediator or mitogen to HSCs and increased BAs in Fgf15^-/- mice leads to enhanced FXR activation in HSCs, subsequently reducing fibrogenesis. In this study, complimentary in vivo and in vitro approaches were used: (1) CCl₄ -induced LF model in wild type (WT), Fgf15^-/- , and Fgf15 transgenic (TG) mice with BA levels modulated by feeding cholestyramine- or cho

SUBMITTER: Schumacher JD 

PROVIDER: S-EPMC6918008 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature