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Fibroblast growth factor 18 stimulates the proliferation of hepatic stellate cells, thereby inducing liver fibrosis

Author

Listed:
  • Yuichi Tsuchiya

    (Toho University
    Toho University)

  • Takao Seki

    (Toho University)

  • Kenta Kobayashi

    (Toho University
    Tokyo University of Science)

  • Sachiko Komazawa-Sakon

    (Toho University)

  • Shigeyuki Shichino

    (Tokyo University of Science)

  • Takashi Nishina

    (Toho University)

  • Kyoko Fukuhara

    (Juntendo University)

  • Kenichi Ikejima

    (Juntendo University)

  • Hidenari Nagai

    (Toho University Omori Medical Center)

  • Yoshinori Igarashi

    (Toho University Omori Medical Center)

  • Satoshi Ueha

    (Tokyo University of Science)

  • Akira Oikawa

    (Kyoto University)

  • Shinya Tsurusaki

    (National Center for Global Health and Medicine
    The University of Tokyo)

  • Soh Yamazaki

    (Toho University)

  • Chiharu Nishiyama

    (Tokyo University of Science)

  • Tetuo Mikami

    (Toho University)

  • Hideo Yagita

    (Juntendo University)

  • Ko Okumura

    (Juntendo University)

  • Taketomo Kido

    (The University of Tokyo)

  • Atsushi Miyajima

    (The University of Tokyo)

  • Kouji Matsushima

    (Tokyo University of Science)

  • Mai Imasaka

    (Hyogo Medical University)

  • Kimi Araki

    (Kumamoto University
    Kumamoto University)

  • Toru Imamura

    (Hoshi University School of Pharmacy and Pharmaceutical Sciences
    National Institute of Advanced Industrial Science and Technology (AIST))

  • Masaki Ohmuraya

    (Hyogo Medical University)

  • Minoru Tanaka

    (National Center for Global Health and Medicine
    The University of Tokyo)

  • Hiroyasu Nakano

    (Toho University)

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.

Suggested Citation

  • Yuichi Tsuchiya & Takao Seki & Kenta Kobayashi & Sachiko Komazawa-Sakon & Shigeyuki Shichino & Takashi Nishina & Kyoko Fukuhara & Kenichi Ikejima & Hidenari Nagai & Yoshinori Igarashi & Satoshi Ueha &, 2023. "Fibroblast growth factor 18 stimulates the proliferation of hepatic stellate cells, thereby inducing liver fibrosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42058-z
    DOI: 10.1038/s41467-023-42058-z
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    References listed on IDEAS

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    1. Suoqin Jin & Christian F. Guerrero-Juarez & Lihua Zhang & Ivan Chang & Raul Ramos & Chen-Hsiang Kuan & Peggy Myung & Maksim V. Plikus & Qing Nie, 2021. "Inference and analysis of cell-cell communication using CellChat," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    2. P. Ramachandran & R. Dobie & J. R. Wilson-Kanamori & E. F. Dora & B. E. P. Henderson & N. T. Luu & J. R. Portman & K. P. Matchett & M. Brice & J. A. Marwick & R. S. Taylor & M. Efremova & R. Vento-Tor, 2019. "Resolving the fibrotic niche of human liver cirrhosis at single-cell level," Nature, Nature, vol. 575(7783), pages 512-518, November.
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