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.

中文翻译：

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miR-485-5p通过靶向cdc42和Rac1抑制雪旺细胞增殖和髓鞘形成。

雪旺细胞是周围神经系统的关键元素，在周围神经损伤后起着重要的作用。近年来，已发现miR-485-5p在神经系统疾病中的作用。但是，miR-485-5p与周围神经损伤的关系仍然未知。对小鼠进行坐骨神经挤压以模仿周围神经损伤，并通过实时PCR检测坐骨神经残端中miR-485-5p的表达。使用miR-485-5p模拟物和miR-485-5p抑制剂转染后，使用BrdU分析法分析雪旺细胞的增殖。通过评估环磷酸一腺苷（cAMP）诱导的髓磷脂相关蛋白（包括Krox20和MBP）的水平来确定miR-485-5p对雪旺氏细胞髓鞘形成的影响，以及通过抗MBP抗体的免疫染色对Schwann细胞和背根神经节（DRG）神经元进行共培养。miR-485-5p的调控机制通过生物信息学分析，荧光素酶报告基因分析，实时荧光定量PCR和Western印迹进行了测定。我们发现神经损伤后miR-485-5p表达下调。miR-485-5p模拟物显着抑制了Schwann细胞中Krox20和MBP的增殖和cAMP诱导的表达水平。相反，miR-485-5p抑制剂促进了雪旺氏细胞中的这些变化。同样，miR-485-5p抑制剂可升高MBP阳性髓鞘纤维。Cdc42和Rac1是Schwann细胞中miR-485-5p的靶标。cdc42的下调逆转了miR-485-5p抑制剂对雪旺细胞增殖的作用。降低Rac1表达减弱了miR-485-5p沉默对雪旺氏细胞髓鞘形成的影响。总之，这项研究表明miR-485-5p通过靶向cdc42和Rac1抑制了雪旺氏细胞的增殖和髓鞘形成。这可能为周围神经损伤的治疗提供一种新的方法。