Novel protein C6ORF120 promotes liver fibrosis by activating hepatic stellate cells through the PI3K/Akt/mTOR pathway
Xin Wang, Hui Liu, Yuqi Wang, Peng Wang, Yunyun Yi, Yingying Lin, Xin Li
Abstract
Abstract Background and Aim The 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). Methods In 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. Results C6orf120 −/− 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. Conclusion C6ORF120 could activate hepatic stellate cells and promote hepatic fibrosis via the PI3K/Akt/mTOR signaling pathway.