Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, PR China; Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: [Email]
Liver regeneration is a fundamental biological process required for sustaining body homeostasis and restoring liver function after injury. Emerging evidence demonstrates that cytokines, growth factors and multiple signaling pathways contribute to liver regeneration. Mammalian target of rapamycin complex 2 (mTORC2) was identified to regulate cell metabolism, proliferation and survival. The major substrates for mTORC2 are the AGC-family members of kinases, including AKT, SGK and PKC-α. Here, we investigated the functional roles of mTORC2 during liver regeneration. For this purpose, we performed partial hepatectomy (PHx) in liver specific Rictor (the pivotal unit of mTORC2 complex) knockout (RictorLKO) and wild-type (Rictorfl/fl) mice. We discovered that Rictor deficient mice are more intolerant to PHx and display higher mortality after PHx. Mechanistically, loss of Rictor resulted in decreased Akt phosphorylation, leading to a delay in hepatocyte proliferation and lipid droplets formation along liver regeneration. Overall, these results indicate an essential role of the mTORC2 signaling pathway during liver regeneration.