Longevity & AgingGDF10 Calms Scar-Forming Liver Cells and Reverses Fibrosis in Mice
Liver fibrosis determines outcomes in MASH, yet no approved drugs target it directly. This preclinical study examined GDF10, a TGF-β superfamily member found mainly in hepatic stellate cells (HSCs), the cells that produce scar tissue. Its expression fell as fibrosis worsened in mouse models and human cirrhotic livers. Boosting Gdf10 with AAV vectors in diet-induced MASH and CCl4 fibrosis models reduced collagen deposition, liver enzymes (ALT/AST), and fibrogenic genes without changing glucose or lipid metabolism. Mechanistically, GDF10 competes with TGF-β1 for the TGF-β receptor 2, limiting SMAD2/3 activation and pushing activated HSCs toward a quiescent, less glycolytic state. The team also built liver-targeted lipid nanoparticles carrying Gdf10 mRNA that reached HSCs and reversed fibrosis in multiple animal models. Findings are preclinical and require human validation.
