Fibroblast growth factor 7 inhibits hepatic steatosis, inflammation and fibrosis in murine models of on non-alcoholic steatohepatitis

The activation of hepatic stellate cells (HSCs) is the key event of hepatic fibrosis, and we have previously shown that fibroblast growth factor 7 (FGF7) expression is de novo expressed during HSC-activation while its highly specific receptor FGFR2IIIb is exclusively expressed on hepatocytes in the liver.

The aim of this study was characterize the function of FGF7 in chronic liver disease with a focus on non-alcoholic steatohepatitis (NASH).

Methods and Results: FGF7-deficient (FGF7-ko) and wildtype (wt) control mice were subjected to two different NASH-models, namely feeding a (i) methionine-choline deficient diet (MCD) or (ii) high-fat diet (HFD). In both models FGF7-deficient mice exhibited significantly elevated hepatic steatosis. Furthermore, FGF7-deficient mice showed higher serum transaminases, histological inflammation and hepatic TNF and IL-1 expression compared to wt-mice. Further, FGF7-ko showed advanced HSC activation, profibrogenic gene expression (Collagen I and TGF-beta) and fibrosis. In contrast, application of recombinant FGF7 to wildtype mice ameliorated enhanced stetaosis as well as inflammation and fibrosis in the MCD-model.

Summary and conclusion: Recombinant FGF7 therapy is already approved in the US and Europe for decreasing the incidence and duration of oral mucositis, and has been shown to be safe. Furthermore, we have previously shown that FGFR2IIIb, which is the exclusive receptor for FGF7, acts as a tumor-suppressor in hepatocellular carcinoma. Thus, FGF7 appears as promising novel anti-fibrogenic drug for the treatment of hepatic fibrosis in patients with chronic liver disease especially NASH.

Corresponding author: Hellerbrand, Claus

E-Mail: [e-mail]