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MicroRNA‐144 promotes remote limb ischemic preconditioning-mediated neuroprotection against ischemic stroke via PTEN/Akt pathway

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Abstract

Ischemic stroke is a refractory disease generally caused by cerebral ischemic injury. Remote ischemic preconditioning (RIPC) caused by transient ischemia and reperfusion of the femoral artery exerts a protective effect on ischemic stroke-induced brain injury. This study was designed to investigate the potential molecular mechanism of RIPC-mediated neuroprotection, namely, the biological effects of microRNA-144 on RIPC in mice with ischemic stroke and its effects on PTEN and Akt signaling pathways. Healthy adult C57BL6 mice were selected for the establishment of middle cerebral artery occlusion (MCAO). One hour before the start, remote ischemic preconditioning of limbs was performed in mice. Brain edema and infarct volume were measured. The expressions of microRNA-144, PTEN, and Akt were measured. The results showed that, compared with MCAO group, the RIPC group protected mice from cerebral ischemia–reperfusion injury, systemic accumulation of inflammatory cytokines, and accelerated apoptosis of parenchymal cells. In RIPC group, PTEN expression decreased, and mir-144 and Akt expression increased. The level of phosphorylated PTEN in the transfected microRNA-144 inhibitor group increased and the level of phosphorylated Akt reduced significantly. In conclusion, our results suggest that microRNA-144 may play a protective role in remote ischemic pretreatment by downregulating PTEN and upregulating Akt, suggesting that microRNA-144 via PTEN/Akt pathway may be of therapeutic significance in ischemic stroke.

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Acknowledgements

This work was funded by the Jiangsu Students’ Platform for innovation and entrepreneurship training program (201810313035Y), National Demonstration Center for Experimental Basic Medical Science Education (Xuzhou Medical University).

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Author notes

  1. Si-Jin Zhong and Miao-Miao Cui have contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical, Xuzhou Medical University, Xuzhou, 221004, China

    Si-Jin Zhong & Xue-Yan Cao

  2. Department of Genetics, Xuzhou Medical University, Xuzhou, 221004, China

    Miao-Miao Cui & Xian-Ru Wen

  3. Medical Technology School, Xuzhou Medical University, Xuzhou, 221004, China

    Yu-Ting Gao

  4. Department of Rehabilitation and National Clinical Research Base of Traditional Chinese Medicine, The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, China

    Bin Chen

Authors
  1. Si-Jin Zhong
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  2. Miao-Miao Cui
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  3. Yu-Ting Gao
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  4. Xue-Yan Cao
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  5. Bin Chen
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Contributions

SJZ, MMC and YTG contributed to the conception and design of the study. XYC analyzed the data. BC and XRW and BC drafted the manuscript and figures. Final approval of the version to be published: All authors.

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Correspondence to Bin Chen or Xian-Ru Wen.

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The authors declare that they have no conflict of interest.

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The experimental procedures were strictly carried out in accordance with the Care and Use of Laboratory Animals Guide from the Ministry of Public Health of China, and approved by the medical ethics committee of Xuzhou Medical University.

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Zhong, SJ., Cui, MM., Gao, YT. et al. MicroRNA‐144 promotes remote limb ischemic preconditioning-mediated neuroprotection against ischemic stroke via PTEN/Akt pathway. Acta Neurol Belg 121, 95–106 (2021). https://doi.org/10.1007/s13760-020-01500-5

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  • DOI: https://doi.org/10.1007/s13760-020-01500-5

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