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Mild hypothermia ameliorates hepatic ischemia reperfusion injury by inducing RBM3 expression

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Abstract

Liver ischemia reperfusion injury (IRI) is a serious complication of certain liver surgeries, and it is difficult to prevent. As a potential drug-free treatment, mild hypothermia has been shown to promote positive outcomes in patients with IRI. However, the protective mechanism remains unclear. We established in vivo and in vitro models of hepatic ischemia reperfusion (IR) and mild hypothermia pretreatment. Hepatocytes were transfected with RNA-binding motif protein 3 (RBM3) overexpression plasmids, and IR was performed. Cell, culture medium, blood and tissue samples were collected to assess hepatic injury, oxidative stress, apoptosis and changes in RBM3 expression in the liver. Upregulation of RBM3 expression by mild hypothermia reduced the aminotransferase release, liver tissue injury and mitochondrial injury induced by liver IR. Hepatic IR-induced p38 and c-Jun N-terminal kinase (JNK) signaling pathway activation, oxidative stress injury and apoptosis could be greatly reversed by mild hypothermia. Overexpression of RBM3 mimicked the hepatoprotective effect of mild hypothermia. Mild hypothermia protects the liver from ischemia reperfusion-induced p38 and JNK signaling pathway activation, oxidative stress injury and apoptosis through the upregulation of RBM3 expression.

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Data availability

The datasets used and analyzed during the current study available from the corresponding author on reasonable request.

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Acknowledgements

Not applicable.

Funding

This study was supported by National Natural Science Foundation of China (No:82060122). Natural Science Foundation of Jiangxi Province (no. 20212BAB206027, 20212BAG7001). Project of Jiangxi Provincial of Education Department (GJJ180014, GJJ200142). Project of Chinese medicine Administration of Jiangxi Provincial of Health Commission (2019A304, 2018A366), Project of Jiangxi Provincial of Health Commission (202130242, 20175074).

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Author notes

  1. Qi Xiao and Yuan Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Transplantation, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China

    Qi Xiao, Yuan Liu, XingJian Zhang & JianSheng Xiao

  2. Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China

    ZhongZhong Liu & QiFa Ye

  3. Department of Immunology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China

    BiQi Fu

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  1. Qi Xiao
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Contributions

QX participated in the performance of the research design, data analysis and article writing. YL prepared Fig. 1–7, XJZ and ZZL participated in the performance of data analysis, JSX participated in the performance of the research. QFY and BQF participated in research design, discussion, and article revision. All authors reviewed the manuscript.

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Correspondence to QiFa Ye or BiQi Fu.

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the protocols of animal experiments were approved by the Animal Ethics Committee of Wuhan University.

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Xiao, Q., Liu, Y., Zhang, X. et al. Mild hypothermia ameliorates hepatic ischemia reperfusion injury by inducing RBM3 expression. Apoptosis 27, 899–912 (2022). https://doi.org/10.1007/s10495-022-01757-6

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