PP2Acα positively regulates the termination of liver regeneration in mice through the AKT/GSK3β/Cyclin D1 pathway

Lai, Shanshan; Zhao, Dandan; Cao, Peng; Luo, Ouyang; Chen, Weibo; Liu, Jia; Jiang, Erhui; Yu, Zihan; Lee, Gina; Li, Jing; Yu, Decai; Xu, Xiaojun; Zhu, Min–Sheng; Gao, Xiang; Li, Chao‐Jun; Xue, Bin

doi:10.1016/j.jhep.2015.09.025

Cited by 29 publications

(33 citation statements)

References 38 publications

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“…The liver is highly susceptible to damage by physical and chemical factors. In essence, liver regeneration process is a protective mechanism by which liver tissue recovers from physical or chemical injury . whereas the precise molecular mechanism of liver regeneration has not yet been clarified.…”

Section: Discussionmentioning

confidence: 99%

PLCγ2 promotes apoptosis while inhibits proliferation in rat hepatocytes through PKCD/JNK MAPK and PKCD/p38 MAPK signalling

Chen

et al. 2018

Cell Proliferation

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Section: Discussionmentioning

confidence: 99%

PLCγ2 promotes apoptosis while inhibits proliferation in rat hepatocytes through PKCD/JNK MAPK and PKCD/p38 MAPK signalling

Chen

et al. 2018

Cell Proliferation

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“…The results suggested that PI3K-Akt-GSK3β signal pathway might play an important role in the pre-protective effect of mild hypothermia. PI3K-Akt-GSK3β signal pathway has been demonstrated to be essential for the recovery of liver cell injury by some groups [43–47]. The pathway also has been indicated to hold the ability to regulate the protective effect of mild hypothermia against ischaemia/reperfusion injury.…”

Section: Discussionmentioning

confidence: 99%

Effect of mild hypothermia preconditioning against low temperature (4°C) induced rat liver cell injury in vitro

et al. 2017

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Bioartificial liver holds special position in the field of regenerative medicine, and cold environment at 4℃ is widely used for the short storage of both organ and liver cell for later application. However, the disadvantages of such cold storage could influence cell viability and lead to cell apoptosis in different degrees. In this study, we mainly explore the pre-protective effect of mild hypothermia against low temperature (4℃)-induced rat liver cell injury in vitro. Our results indicated that the precondition with mild hypothermia could increase cell viability, such as cell proliferation, LDH regulation and glycogen synthesis ability of liver cell. The precondition also decreased the ROS production and relieved cell apoptosis in liver cells. Compared with the model group, the mitochondrial membrane potential was restored in the mild hypothermia group, as well as the mitochondrial membrane permeability transition pore opening, indicating that the therapeutic mechanism was related to mitochondrial protection. Further analysis showed that PI3K-Akt-GSK3β signal pathway might be associated with the pre-protective effect of mild hypothermia. Thus, our study suggested that the precondition with mild hypothermia hold the protective effect for liver cell in cold environment, and further developed a novel strategy for the storage of liver seed cells, even bioartificial liver.

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“…In addition, certain types of nanoparticle carriers have been used as a new tool for the treatment of liver diseases 6 , 7 . Changing the expression of key genes and transcription factors, such as osteopontin (OPN), TGF beta and PP2Acα 8 – 10 , can also increase hepatocyte proliferation and liver regeneration. However, changing the expression of key genes and transcription factors may also cause many problems, such as tumorigenesis and insertional mutagenesis 11 .…”

Section: Introductionmentioning

confidence: 99%

Exosome-Mimetic Nanovesicles from Hepatocytes promote hepatocyte proliferation in vitro and liver regeneration in vivo

Wang

et al. 2018

Sci Rep

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The liver has great regenerative capacity after functional mass loss caused by injury or disease. Many studies have shown that primary hepatocyte-derived exosomes, which can deliver biological information between cells, promote the regenerative process of the liver. However, the yield of exosomes is very limited. Recent studies have demonstrated that exosome-mimetic nanovesicles (NVs) can be prepared from cells with almost 100 times the production yield compared with exosomes. Thus, this study investigated the therapeutic capacity of exosome-mimetic NVs from primary hepatocytes in liver regeneration. Exosome-mimetic NVs were prepared by serial extrusions of cells through polycarbonate membranes, and the yield of these NVs was more than 100 times that of exosomes. The data indicated that the NVs could promote hepatocyte proliferation and liver regeneration by significantly enhancing the content of sphingosine kinase 2 in recipient cells. To the best of our knowledge, this is the first time that exosome-mimetic NVs from primary hepatocytes have been prepared, and these NVs have components similar to exosomes from primary hepatocytes and, in some respects, biofunctions similar to exosomes. Strategies inspired by this study may lead to substitution of exosomes with exosome-mimetic NVs for biofunctional purposes, including utilization in tissue repair and regeneration.

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PP2Acα positively regulates the termination of liver regeneration in mice through the AKT/GSK3β/Cyclin D1 pathway

Abstract: PP2Acα plays an essential role in the proper termination of LR via the AKT/GSK3β/Cyclin D1 pathway. Our findings enrich the understanding of the molecular mechanism that controls the termination of LR and provides a potential therapeutic target for treating liver injury.

Cited by 29 publications

References 38 publications

PLCγ2 promotes apoptosis while inhibits proliferation in rat hepatocytes through PKCD/JNK MAPK and PKCD/p38 MAPK signalling

PLCγ2 promotes apoptosis while inhibits proliferation in rat hepatocytes through PKCD/JNK MAPK and PKCD/p38 MAPK signalling

Effect of mild hypothermia preconditioning against low temperature (4°C) induced rat liver cell injury in vitro

Exosome-Mimetic Nanovesicles from Hepatocytes promote hepatocyte proliferation in vitro and liver regeneration in vivo

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