Melatonin promotes Schwann cell dedifferentiation and proliferation through the Ras/Raf/ERK and MAPK pathways, and glial cell‑derived neurotrophic factor expression
- Yee Lian Tiong
- Khuen Yen Ng
- Rhun Yian Koh
- Gnanajothy Ponnudurai
- Soi Moi Chye
Affiliations: School of Postgraduate, International Medical University, Kuala Lumpur 57000, Malaysia, School of Pharmacy, Monash University Malaysia, Subang Jaya, Selangor 47500, Malaysia, School of Health Science, International Medical University, Kuala Lumpur 57000, Malaysia, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
- Published online on: August 26, 2020 https://doi.org/10.3892/etm.2020.9143
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Upon peripheral nerve injury (PNI), continuous proliferation of Schwann cells is critical for axon regeneration and tubular reconstruction for nerve regeneration. Melatonin is a hormone that is able to induce proliferation in various cell types. In the present study, the effects of melatonin on promoting Schwann cell proliferation and the molecular mechanism involved were investigated. The present results showed that melatonin enhanced the melatonin receptors (MT1 and MT2) expression in Schwann cells. Melatonin induced Schwann cell dedifferentiation into progenitor‑like Schwann cells, as observed by immunofluorescence staining, which showed Sox2 marker expression. In addition, melatonin enhanced Schwann cell proliferation, mediated by the upregulation of glial cell‑derived neurotropic factor (GNDF) and protein kinase C (PKC). Furthermore, the Ras/Raf/ERK and MAPK signaling pathways were also involved in Schwann cell dedifferentiation and proliferation. In conclusion, melatonin induced Schwann cell dedifferentiation and proliferation via the Ras/Raf/ERK, MAPK and GDNF/PKC pathways. The present results suggested that melatonin could be used to enhance the recovery of PNI.