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RESEARCH ARTICLE
Year : 2018  |  Volume : 13  |  Issue : 7  |  Page : 1253-1262

Spatiotemporal microRNA profile in peripheral nerve regeneration: miR-138 targets vimentin and inhibits Schwann cell migration and proliferation


1 Department of Translational Research, Lahey Hospital & Medical Center, Burlington, MA, USA
2 Tissue Engineering Laboratory, Lahey Hospital & Medical Center, Burlington, MA, USA
3 Department of Plastic and Reconstructive Surgery, Lahey Hospital & Medical Center, Burlington, MA, USA
4 Tissue Engineering Laboratory; Department of Plastic and Reconstructive Surgery, Lahey Hospital & Medical Center, Burlington, MA, USA

Correspondence Address:
Kimberly M Rieger-Christ
Department of Translational Research, Lahey Hospital & Medical Center, Burlington, MA
USA
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Source of Support: This study was supported by the Leisa V. Clayton Foundation, Conflict of Interest: None


DOI: 10.4103/1673-5374.235073

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While the peripheral nervous system has regenerative ability, restoration of sufficient function remains a challenge. Vimentin has been shown to be localized in axonal growth fronts and associated with nerve regeneration, including myelination, neuroplasticity, kinase signaling in nerve axoplasm, and cell migration; however, the mechanisms regulating its expression within Schwann cell (SC) remain unexplored. The aim of this study was to profile the spatial and temporal expression profile of microRNA (miRNA) in a regenerating rat sciatic nerve after transection, and explore the potential role of miR-138-5p targeting vimentin in SC proliferation and migration. A rat sciatic nerve transection model, utilizing a polyethylene nerve guide, was used to investigate miRNA expression at 7, 14, 30, 60, and 90 days during nerve regeneration. Relative levels of miRNA expression were determined using microarray analysis and subsequently validated with quantitative real-time polymerase chain reaction. In vitro assays were conducted with cultured Schwann cells transfected with miRNA mimics and assessed for migratory and proliferative potential. The top seven dysregulated miRNAs reported in this study have been implicated in cell migration elsewhere, and GO and KEGG analyses predicted activities essential to wound healing. Transfection of one of these, miRNA-138-5p, into SCs reduced cell migration and proliferation. miR-138-5p has been shown to directly target vimentin in cancer cells, and the luciferase assay performed here in rat Schwann cells confirmed it. These results detail a role of miR-138-5p in rat peripheral nerve regeneration and expand on reports of it as an important regulator in the peripheral nervous system.


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