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MicroRNA-139-5p Promotes Functional Recovery and Reduces Pain Hypersensitivity in Mice with Spinal Cord Injury by Targeting Mammalian Sterile 20-like Kinase 1

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Abstract

Currently, there is no cure for spinal cord injury (SCI), a heavy burden on patients physiology and psychology. We found that microRNA-139-5p (miR-139-5p) expression was significantly downregulated in damaged spinal cords in mice. So, we aimed to test the effect of treatment with miR-139-5p on functional recovery and neuropathic pain in mice with SCI and investigate the underlying mechanism. The luciferase reporter assay revealed that miR-139-5p directly targeted mammalian sterile 20-like kinase 1 (Mst1), and miR-139-5p treatment suppressed Mst1 protein expression in damaged spinal cords of mice. Wild-type mice and Mst1(−/−) mice were exposed to SCI and treated with miR-139-5p agomir via intrathecal infusion. Treatment of SCI mice with miR-139-5p accelerated locomotor functional recovery, reduced hypersensitivities to mechanical and thermal stimulations, and promoted neuronal survival in damaged spinal cords. Treatment with miR-139-5p enhanced phosphorylation of adenosine monophosphate-activated protein kinase alpha (AMPKα), improved mitochondrial function, and suppressed NF-κB-related inflammation in damaged spinal cords. Deficiency of Mst1 had similar benefits in mice with SCI. Furthermore, miR-139-5p treatment did not provide further protection in Mst1(−/−) mice against SCI. In conclusion, miR-139-5p treatment enhanced functional recovery and reduced pain hypersensitivity in mice with SCI, possibly through targeting Mst1.

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Acknowledgements

This work was supported by grants from Planned Science and Technology Project of Suzhou city (SS201611 to Yongming Sun).

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  1. Panfeng Wang and Yuntong Zhang have contributed equally to the work.

Authors and Affiliations

  1. War and Traumat Emergency Centre, Changhai Hospital, Navy Military Medical University, Changhai Road 168, Shanghai, 200433, China

    Panfeng Wang, Yuntong Zhang, Yan Xia, Dayuan Xu, Hongrui Wang & Shuogui Xu

  2. Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Sanxiang Road 1055, Suzhou, 215004, China

    Panfeng Wang, Dong Liu & Yongming Sun

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  1. Panfeng Wang
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Wang, P., Zhang, Y., Xia, Y. et al. MicroRNA-139-5p Promotes Functional Recovery and Reduces Pain Hypersensitivity in Mice with Spinal Cord Injury by Targeting Mammalian Sterile 20-like Kinase 1. Neurochem Res 46, 349–357 (2021). https://doi.org/10.1007/s11064-020-03170-4

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