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.

mTORC2 Signaling Is Necessary for Timely Liver Regeneration after Partial Hepatectomy / Xu, M.; Wang, H.; Wang, J.; Burhan, D.; Shang, R.; Wang, P.; Zhou, Y.; Li, R.; Liang, B.; Evert, K.; Utpatel, K.; Xu, Z.; Song, X.; Che, L.; Calvisi, D. F.; Wang, B.; Chen, X.; Zeng, Y.; Chen, X.. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - 190:4(2020), pp. 817-829. [10.1016/j.ajpath.2019.12.010]

mTORC2 Signaling Is Necessary for Timely Liver Regeneration after Partial Hepatectomy

Calvisi D. F.;
2020-01-01

Abstract

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.
2020
mTORC2 Signaling Is Necessary for Timely Liver Regeneration after Partial Hepatectomy / Xu, M.; Wang, H.; Wang, J.; Burhan, D.; Shang, R.; Wang, P.; Zhou, Y.; Li, R.; Liang, B.; Evert, K.; Utpatel, K.; Xu, Z.; Song, X.; Che, L.; Calvisi, D. F.; Wang, B.; Chen, X.; Zeng, Y.; Chen, X.. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - 190:4(2020), pp. 817-829. [10.1016/j.ajpath.2019.12.010]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/240485
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