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Dysregulated miR-29a-3p/PMP22 Modulates Schwann Cell Proliferation and Migration During Peripheral Nerve Regeneration

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Abstract

Schwann cells switch to a repair phenotype following peripheral nerve injury and create a favorable microenvironment to drive nerve repair. Many microRNAs (miRNAs) are differentially expressed in the injured peripheral nerves and play essential roles in regulating Schwann cell behaviors. Here, we examine the temporal expression patterns of miR-29a-3p after peripheral nerve injury and demonstrate significant up-regulation of miR-29a-3p in injured sciatic nerves. Elevated miR-29a-3p inhibits Schwann cell proliferation and migration, while suppressed miR-29a-3p executes reverse effects. In vivo injection of miR-29a-3p agomir to rat sciatic nerves hinders the proliferation and migration of Schwann cells, delays the elongation and myelination of axons, and retards the functional recovery of injured nerves. Mechanistically, miR-29a-3p modulates Schwann cell activities via negatively regulating peripheral myelin protein 22 (PMP22), and PMP22 extensively affects Schwann cell metabolism. Our results disclose the vital role of miR-29a-3p/PMP22 in regulating Schwann cell phenotype following sciatic nerve injury and shed light on the mechanistic basis of peripheral nerve regeneration.

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Data Availability

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

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Funding

This study was supported by Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX21_3076] and Priority Academic Program Development of Jiangsu Higher Education Institutions [PAPD].

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Authors and Affiliations

  1. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, 226001, Jiangsu, China

    Yinying Shen, Zhangchun Cheng, Sailing Chen, Yunsong Zhang & Sheng Yi

  2. School of Life Sciences, Nantong University, Nantong, 226001, Jiangsu, China

    Qi Chen

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  1. Yinying Shen
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Contributions

Conceived and designed the experiments: S.Y. Experiment conductance and data analyses: Y.S., Z.C., S.C., Y.Z. Contributed reagents/materials/analysis tools: Q.C., S.Y. Wrote the manuscript: Q.C., S.Y.

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Correspondence to Qi Chen or Sheng Yi.

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Animal experiments were approved ethically by the Administration Committee of Experimental Animals, Jiangsu, China, and conducted in accordance with Institutional Animal Care Guidelines of Nantong University.

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Fig. S1

Immunostaining of the sciatic nerves of agomir control or miR-29a-3p agomir-injected rats underwent sham surgery. (A and B) S100 staining of the sciatic nerves of rats subjected to (A) agomir control or (B) miR-29a-3p agomir injection 2 days prior to sham surgery. (C and D) NF staining of the sciatic nerves of rats subjected to (C) agomir control or (D) miR-29a-3p agomir injection 2 days prior to sham surgery. Agomir con represents agomir control. Red color represents S100β staining, green color represents NF staining, and blue color represents nucleus staining. Scale bar represents 1000 μm

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Shen, Y., Cheng, Z., Chen, S. et al. Dysregulated miR-29a-3p/PMP22 Modulates Schwann Cell Proliferation and Migration During Peripheral Nerve Regeneration. Mol Neurobiol 59, 1058–1072 (2022). https://doi.org/10.1007/s12035-021-02589-2

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