GDF10 attenuates MASH progression by restoring quiescent hepatic stellate cells via competitive inhibition of TGF-β/SMAD2 signaling.

ABSTRACT: Liver fibrosis has emerged as the primary determinant of outcomes in metabolic dysfunction-associated steatohepatitis (MASH). Quiescent hepatic stellate cells (HSCs) differentiate into activated HSCs or myofibroblasts, which drives liver fibrosis and contribute to the progressive loss of hepatic function. MASH with progressive fibrosis lacks effective therapies due to incomplete understanding of HSCs regulation. Here, we identify growth differentiation factor 10 (GDF10) as a master regulator of HSCs quiescence that ameliorates fibrosis through shifting HSC functions to restore HSC balance of transcriptional and metabolic reprogramming. Single-cell RNA sequencing revealed HSC-specific Gdf10 expression inversely correlated with fibrotic activation. In murine models of diet-induced MAS

SUBMITTER: Peng Y 

PROVIDER: S-EPMC12631229 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature