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Fibroblast growth factor 18 stimulates the proliferation of hepatic stellate cells, thereby inducing liver fibrosis
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Fibroblast growth factor 18 stimulates the proliferation of hepatic stellate cells, thereby inducing liver fibrosis
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Journal Article
Fibroblast growth factor 18 stimulates the proliferation of hepatic stellate cells, thereby inducing liver fibrosis
2023
Overview
Liver fibrosis results from chronic liver injury triggered by factors such as viral infection, excess alcohol intake, and lipid accumulation. However, the mechanisms underlying liver fibrosis are not fully understood. Here, we demonstrate that the expression of
fibroblast growth factor 18
(
Fgf18
) is elevated in mouse livers following the induction of chronic liver fibrosis models. Deletion of
Fgf18
in hepatocytes attenuates liver fibrosis; conversely, overexpression of
Fgf18
promotes liver fibrosis. Single-cell RNA sequencing reveals that overexpression of
Fgf18
in hepatocytes results in an increase in the number of
Lrat
+
hepatic stellate cells (HSCs), thereby inducing fibrosis. Mechanistically, FGF18 stimulates the proliferation of HSCs by inducing the expression of
Ccnd1
. Moreover, the expression of
FGF18
is correlated with the expression of profibrotic genes, such as
COL1A1
and
ACTA2
, in human liver biopsy samples. Thus, FGF18 promotes liver fibrosis and could serve as a therapeutic target to treat liver fibrosis.
Fibroblast growth factor (FGF)18 plays pleiotropic roles, including bone development and carcinogenesis, however, its precise role in liver fibrosis remains incompletely understood. Here, the authors show that FGF18 promotes liver fibrosis by stimulating hepatic stellate cell proliferation, without concomitant upregulation of profibrotic genes.
