Department of General Surgery, The Second Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, PR China; Department of Bioengineering and Therapeutic Sciences, Liver Center, University of California, San Francisco, California.
Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, PR China; Department of Bioengineering and Therapeutic Sciences, Liver Center, University of California, San Francisco, California; Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, PR China; Department of General Surgery, The Second Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, PR China.
Am J Pathol. 2020 Apr;190(4):817-829. doi: 10.1016/j.ajpath.2019.12.010. Epub 2020 Feb 5.
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) regulates cell metabolism, proliferation and survival. The major substrates for mTORC2 are the AGC family members of kinases, including AKT, SGK, and PKC-α. We investigated the functional roles of mTORC2 during liver regeneration. Partial hepatectomy (PHx) was performed in liver-specific Rictor (the pivotal unit of mTORC2 complex) knockout (Rictor) and wild-type (Rictor) mice. Rictor-deficient mice were found to be more intolerant to PHx and displayed 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.
肝脏再生是维持体内平衡和损伤后恢复肝功能所必需的基本生物学过程。新出现的证据表明，细胞因子、生长因子和多种信号通路有助于肝脏再生。雷帕霉素复合物 2（mTORC2）调节细胞代谢、增殖和存活。mTORC2 的主要底物是 AGC 家族激酶成员，包括 AKT、SGK 和 PKC-α。我们研究了 mTORC2 在肝脏再生过程中的功能作用。在肝特异性 Rictor（mTORC2 复合物的关键单元）敲除（Rictor）和野生型（Rictor）小鼠中进行部分肝切除术（PHx）。结果发现，Rictor 缺失的小鼠对 PHx 的耐受性较差，PHx 后死亡率更高。在机制上，Rictor 的缺失导致 Akt 磷酸化减少，导致肝细胞增殖和肝再生过程中脂质滴形成延迟。总的来说，这些结果表明 mTORC2 信号通路在肝脏再生过程中起着重要作用。
