Intercellular communication between hepatic stellate cells and myofibroblasts mediated by osteopontin and FGF18 promotes liver fibrosis.

ABSTRACT: 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 r

SUBMITTER: Seki T 

PROVIDER: S-EPMC12269570 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature