Spatiotemporal microRNA profile in peripheral nerve regeneration: miR-138 targets vimentin and inhibits Schwann cell migration and proliferation
| Autor: | Kimberly M. Rieger-Christ, Evan W Beatty, Bryan J Cicuto, Travis Sullivan, David J. Bryan, Litchfield C Robert, Shannon E Morgan, Patrick Teebagy, Peter K Nowd |
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| Rok vydání: | 2018 |
| Předmět: |
non-coding RNA
Schwann cell wound healing Vimentin lcsh:RC346-429 Kyoto Encyclopedia of Genes and Genomes pathways 03 medical and health sciences neural regeneration nerve guide sciatic nerve transection peripheral nerve injury Gene Ontology processes microarray luciferase assay 0302 clinical medicine Developmental Neuroscience medicine lcsh:Neurology. Diseases of the nervous system biology Regeneration (biology) Schwann cell migration Cell migration Cell biology medicine.anatomical_structure nervous system 030220 oncology & carcinogenesis Peripheral nervous system Peripheral nerve injury biology.protein Sciatic nerve 030217 neurology & neurosurgery Research Article |
| Zdroj: | Neural Regeneration Research, Vol 13, Iss 7, Pp 1253-1262 (2018) Neural Regeneration Research |
| ISSN: | 1673-5374 |
| DOI: | 10.4103/1673-5374.235073 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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