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Hypoxia-Induced Upregulation of miR-132 Promotes Schwann Cell Migration After Sciatic Nerve Injury by Targeting PRKAG3

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Abstract

Following peripheral nerve injury, hypoxia is formed as a result of defects in blood supply at the injury site. Despite accumulating evidence on the effects of microRNAs (miRNAs) on phenotype modulation of Schwann cells (SCs) after peripheral nerve injury, the impact of hypoxia on SC behaviors through miRNAs during peripheral nerve regeneration has not been estimated. In this study, we confirmed our previous microarray data on the upregulation of miR-132 after sciatic nerve injury in rats and observed that overexpression of miR-132 significantly promoted cell migration of primary cultured SCs. Interestingly, hypoxia-increased expression of miR-132 also enhanced SC migration while inhibition of miR-132 suppressed hypoxia-induced increase in SC migration. miR-132 downregulated PRKAG3 through binding to its 3′-UTR, and PRKAG3 knockdown compromised the reducing effect of miR-132 inhibition on SC migration under normal or hypoxia condition. Moreover, in vivo injection of miR-132 agomir into rats with sciatic nerve transection accelerated SC migration from the proximal to distal stump. Overall, our results suggest that the hypoxia-induced upregulation of miR-132 could promote SC migration and facilitate peripheral nerve regeneration.

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Acknowledgments

We thank Professor Jie Liu for assistance in manuscript preparation. This work was supported by the National Key Basic Research Program of China [2014CB542202], 863 Program [2012AA020502], National Natural Science Foundation of China [81130080, 31100761, and 31371062], New Century Excellent Talents in University [NCET-12-0742], Graduate Student Scientific and Innovation Research Program of Jiangsu Higher School [KYLX15_1329], and Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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The authors declare that they have no conflicts of interest.

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    Authors and Affiliations

    1. Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China

      Chun Yao, Xiangxiang Shi, Zhanhu Zhang, Songlin Zhou, Tianmei Qian, Yaxian Wang, Fei Ding, Xiaosong Gu & Bin Yu

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    1. Chun Yao
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    Chun Yao and Xiangxiang Shi contributed equally to this work.

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    Yao, C., Shi, X., Zhang, Z. et al. Hypoxia-Induced Upregulation of miR-132 Promotes Schwann Cell Migration After Sciatic Nerve Injury by Targeting PRKAG3. Mol Neurobiol 53, 5129–5139 (2016). https://doi.org/10.1007/s12035-015-9449-y

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