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- Title
Fibroblast growth factor 18 stimulates the proliferation of hepatic stellate cells, thereby inducing liver fibrosis.
- Authors
Tsuchiya, Yuichi; Seki, Takao; Kobayashi, Kenta; Komazawa-Sakon, Sachiko; Shichino, Shigeyuki; Nishina, Takashi; Fukuhara, Kyoko; Ikejima, Kenichi; Nagai, Hidenari; Igarashi, Yoshinori; Ueha, Satoshi; Oikawa, Akira; Tsurusaki, Shinya; Yamazaki, Soh; Nishiyama, Chiharu; Mikami, Tetuo; Yagita, Hideo; Okumura, Ko; Kido, Taketomo; Miyajima, Atsushi
- Abstract
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.
- Subjects
HEPATIC fibrosis; LIVER cells; FIBROBLAST growth factors; LIVER biopsy; BONE growth; RNA sequencing
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-42058-z