セキ　タカオ   Seki Takao   関　崇生    所属   東邦大学  医学部 医学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Intercellular communication between hepatic stellate cells and myofibroblasts mediated by osteopontin and FGF18 promotes liver fibrosis
掲載誌名	正式名：iScience
掲載区分	国外
出版社	Cell Press
巻・号・頁	28(7)
著者・共著者	Takao Seki, Sachiko Komazawa-Sakon, Takashi Nishina, Tetuo Mikami, Hideo Yagita, Katsuhide Okunishi, Minoru Tanaka, Yuichi Tsuchiya, Hiroyasu Nakano
担当区分	筆頭著者
発行年月	2025/06/17
概要	Hepatic stellate cells (HSCs) play a central role in the development of liver fibrosis. We previously showed that fibroblast growth factor 18 (FGF18) promotes liver fibrosis by increasing HSC proliferation. However, the underlying mechanisms remain incompletely understood. Here, we showed that FGF18 efficiently induced osteopontin (Spp1/OPN) expression in culture-activated αSMA+ HSCs, but not in freshly prepared quiescent HSCs. Notably, OPN upregulated profibrotic genes only in quiescent HSCs, suggesting that the activation status of HSCs influences their responsiveness to FGF18 and OPN. Furthermore, FGF18 and TGFβ synergistically increased Spp1/OPN expression in culture-activated αSMA+ HSCs. Immunohistochemical analyses of murine liver fibrosis models revealed that OPN was expressed predominantly in αSMA+ myofibroblasts, but not in desmin+ quiescent HSCs. The cell-cell communication analyses further revealed that myofibroblast-derived Spp1 signaled to HSCs in fibrotic livers. Together, FGF18 initiates a feedforward loop between quiescent and activated αSMA+ HSCs/myofibroblasts via OPN signaling, thereby driving fibrosis progression.