Mst1 attenuates myocardial ischemia/reperfusion injury following heterotopic heart transplantation in mice through regulating Keap1/Nrf2 axis

文献类型： 外文期刊

第一作者： Fei, Qi

作者： Fei, Qi;Liu, Justin;Qiao, Li;Zhang, Meng;Xia, Haidong;Qian, Ban;Lu, Daoqiang;Wu, Di;Wang, Jun;Li, Riwang;Li, Jie;Yang, Fang;Liu, Dahai;Xie, Baiyi;Hui, Wenqiao

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关键词： Heart transplantation; Ischemia reperfusion (I; R) injury; Mst1; Nrf2; ROS production

期刊名称：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS （ 影响因子：3.1； 五年影响因子：3.2 ）

ISSN： 0006-291X

年卷期： 2023 年 644 卷

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收录情况： SCI

摘要： Ischemia reperfusion (I/R) injury remains a frequent adverse event that accompanies heart trans-plantation. Oxidative stress and aberrant production of free radicals were regarded as the culprit of cell death and tissue damage in post-transplant IR injury. Mst1 has been identified as a mediator of oxidative stress and Nrf2 regulates anti-oxidative enzymes, however, the interaction between Mst1 and Nrf2 anti -oxidative stress pathway remains to be clarified in the event of cardiac IR injury. Herein, the model of ischemia-reperfusion injury in heterotopic heart transplantation mice was firstly established.. We observed that cardiac IR induced upregulation of Mst1 and activation of Nrf2/HO-1pathway in mice receiving heterotopic heart transplantation. Further Cobalt dichloride-induced oxidative stress model of RAW264.7 macrophage cells were then established to mimic cardiac I/R injury, results showed that exposure to CoCl2 induced the upregulation of Mst1 and activation of Keap1/Nrf2 pathway, and genetic ablation of Mst-1 and inhibition of Keap1/Nrf2 pathway aggravated oxidative damage in those cells. Additional in vivo study showed that transfection of Mst1 shRNA spurred ROS generation and worsened cardiac damage in IR mice. Meanwhile, Mst1-KD mice receiving heart transplantation showed markedly downregulation of Nrf2, HO-1 yet upregulation of Keap1, indicating diminished protective effect against tissue damage caused by IR probably owing to the frustration of Keap1/Nrf2 pathway. Taken together, our findings demonstrated the protective effect of Mst1 from cardiac IR injury via triggering Keap1/Nrf2 axis and suppressing ROS generation, which shed light on the promising role of Mst1 in transitional man-agement of IR injury resulted from cardiac transplantation.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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