mTORC2 Signaling Is Necessary for Timely Liver Regeneration after Partial Hepatectomy. 2020

Meng Xu, and Haichuan Wang, and Jingxiao Wang, and Deviana Burhan, and Runze Shang, and Pan Wang, and Yi Zhou, and Rong Li, and Bingyong Liang, and Katja Evert, and Kirsten Utpatel, and Zhong Xu, and Xinhua Song, and Li Che, and Diego F Calvisi, and Bruce Wang, and Xi Chen, and Yong Zeng, and Xin Chen
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.

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 (RictorLKO) and wild-type (Rictorfl/fl) 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.

UI MeSH Term Description Entries
D008055 Lipids A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed) Lipid
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008115 Liver Regeneration Repair or renewal of hepatic tissue. Liver Regenerations,Regeneration, Liver,Regenerations, Liver
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D005260 Female Females
D006498 Hepatectomy Excision of all or part of the liver. (Dorland, 28th ed) Hepatectomies
D000076225 Mechanistic Target of Rapamycin Complex 2 A multiprotein complex consisting of mTOR KINASE; MLST8 PROTEIN; rapamycin-insensitive companion of mTOR protein (RICTOR PROTEIN); and PRR5 (proline-rich protein 5). Like mTORC1, it also regulates cell growth and proliferation in response to growth factors but may not be as sensitive to nutrient availability and is insensitive to SIROLIMUS. In contrast to mTORC1, it can regulate the ACTIN CYTOSKELETON through RHO GTPASES to promote the formation of STRESS FIBERS. The mTORC2 complex also plays a critical role in AKT1 PROTEIN KINASE phosphorylation and activation. MTORC-2,TOR Complex 2,TORC2,Target of Rapamycin Complex 2,mTORC2,Complex 2, TOR
D000076226 Rapamycin-Insensitive Companion of mTOR Protein An adaptor protein subunit of MTORC2 COMPLEX. It functions as a structural component and is phosphorylated by RIBOSOMAL PROTEIN S6 KINASES, integrating signals for cell growth and proliferation, especially during embryonic development. RICTOR Protein,Rapamycin Insensitive Companion of mTOR Protein

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