miR-485-5p suppresses Schwann cell proliferation and myelination by targeting cdc42 and Rac1

Abstract

Schwann cells, a crucial element in peripheral nervous system, play important roles after peripheral nerve injury. In recent years, the role of miR-485-5p has been discovered in neurological diseases. However, the involvement of miR-485-5p and peripheral nerve injury remains unknown. Mice were subjected to sciatic nerve crush to mimic peripheral nerve injury and the expression of miR-485-5p was detected in sciatic nerve stumps by real-time PCR. BrdU assay was used to analyze the proliferation of Schwann cells after transfection with miR-485-5p mimic and miR-485-5p inhibitor. The effect of miR-485-5p on Schwann cell myelination was determined by evaluating levels of cyclic adenosine monophosphate (cAMP)-induced myelin-associated proteins, including Krox20 and MBP, as well as the coculture of Schwann cells and dorsal root ganglion (DRG) neurons via immunostaining with anti-MBP antibodies. The regulation mechanism of miR-485-5p was measured by bioinformatics analysis, luciferase reporter assay, and real-time PCR and Western blot. We found miR-485-5p expression was downregulated post nerve injury. miR-485-5p mimic significantly suppressed the proliferation and cAMP-induced expression levels of Krox20 and MBP in Schwann cells. Conversely, miR-485-5p inhibitor promoted these changes in Schwann cells. Also, miR-485-5p inhibitor elevated MBP-positive myelinated fibers. Cdc42 and Rac1 are targets of miR-485-5p in Schwann cells. Downregulation of cdc42 reversed the effect of miR-485-5p inhibitor on the proliferation of Schwann cells. And reducing Rac1 expression attenuated the effect of miR-485-5p silencing on Schwann cell myelination. In conclusion, this study indicated that miR-485-5p suppressed the proliferation and myelination of Schwann cells via targeting cdc42 and Rac1. Which may provide a novel method for the treatment of peripheral nerve injury.

Keywords: Myelination; Proliferation; Rac1; Schwann cells; cdc42; miR-485-5p.