Novel protein C6ORF120 promotes liver fibrosis by activating hepatic stellate cells through the PI3K/Akt/mTOR pathway

Abstract

AbstractBackground and AimThe role of C6ORF120 in promoting CCL4‐induced hepatic fibrosis and its possible mechanisms were explored in C6orf120 knockout rats (C6orf120−/−) and LX‐2 cells (a type of human hepatic stellate cell line).MethodsIn vivo experiments, wild‐type and C6orf120−/− rats were used to investigate the function of C6ORF120. In the in vitro experiments, C6ORF120 recombinant protein (rC6ORF120) at a concentration of 200 ng/mL was used to stimulate LX‐2 cells. Sirius Red staining, Masson staining, western blotting, polymerase chain reaction, immunohistochemistry, and immunofluorescence were used to explore fibrosis‐associated factors.ResultsC6orf120−/− rats showed mild fibrosis and liver injury in the CCL4‐induced liver fibrosis model. Furthermore, RNA‐seq revealed that C6orf120−/− rats had less extracellular matrix deposition and activated stellate cells. Consistent with the in vivo, the rC6ORF120 induced LX‐2 cell activation. Moreover, mechanistic studies revealed that the p‐PI3K/PI3K, p‐Akt/Akt, and p‐mTOR/mTOR levels were significantly elevated and LY294002 (a PI3K/Akt/mTOR typical pathway inhibitor) reversed the function of C6ORF120 in activating LX‐2 cells.ConclusionC6ORF120 could activate hepatic stellate cells and promote hepatic fibrosis via the PI3K/Akt/mTOR signaling pathway.