Secreted folate receptor γ drives fibrogenesis in metabolic dysfunction-associated steatohepatitis by amplifying TGFβ signaling in hepatic stellate cells.

ABSTRACT: Hepatic fibrosis is the primary determinant of mortality in patients with metabolic dysfunction-associated steatohepatitis (MASH). Transforming growth factor-β (TGFβ), a master profibrogenic cytokine, is a promising therapeutic target that has not yet been translated into an effective therapy in part because of liabilities associated with systemic TGFβ antagonism. We have identified that soluble folate receptor γ (FOLR3), which is expressed in humans but not in rodents, is a secreted protein that is elevated in the livers of patients with MASH but not in those with metabolic dysfunction-associated steatotic liver disease, those with type II diabetes, or healthy individuals. Global proteomics showed that FOLR3 was the most highly significant MASH-specific protein and was positively correlat

SUBMITTER: Quinn C 

PROVIDER: S-EPMC11816833 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature