Fibroblast Growth Factor 18 stimulates the proliferation of hepatic stellate cells, thereby inducing liver fibrosis.

A recent study led by Associate Professor Yuichi Tsuchiya from the Department of Biochemistry at Toho University Faculty of Pharmaceutical Sciences, and Professor Hiroyasu Nakano from the Department of Biochemistry at Toho University Faculty of Medicine has uncovered a significant link between Fibroblast Growth Factor 18 (FGF18) and the development of liver fibrosis. The research indicates that FGF18 stimulates the proliferation of hepatic stellate cells, contributing to the progression of liver fibrosis.

A model for FGF18-induced liver fibrosis proposed in this research. In response to various injuries, transforming growth factor-β (TGFβ) is released from different types of cells, such as macrophages engulfing apoptotic hepatocytes. Then, TGFβ induces the production of FGF18 in hepatic stellate cells (HSCs) and hepatocytes. FGF18 then stimulates the proliferation of HSCs. Proliferating HSCs further respond to stimuli derived from scar-associated macrophages and produce collagens and extracellular matrix, thereby promoting liver fibrosis. aHSCs, activated HSCs; PDGF, platelet-derived growth factor; qHSCs, quiescent HSCs; SAMacs, scar-associated macrophages.
Credit: Hiroyasu Nakano

By employing various genetically modified mice and experimental models of liver injury, the research team discovered upregulation of FGF18 in fibrotic livers. They observed that FGF18 promoted the proliferation of hepatic stellate cells in vitro and induced liver fibrosis in vivo. Furthermore, the team identified a correlation between the expressions of FGF18 and profibrotic genes in human biopsy samples. These findings strongly indicate that FGF18 plays a pivotal role in the progression of liver fibrosis.

The findings propose a potential therapeutic target for controlling liver fibrosis in chronic hepatitis by focusing on inhibiting or modulating FGF18. This discovery could pave the way for novel approaches to treating liver fibrosis, offering hope for patients with chronic hepatitis.

The results of the research were published in the scientific journal Nature Communications on October 9, 2023.

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