Investigating the Mechanism by Which RMRP Regulates Diabetic Peripheral Neuropathy via the miR-3142.

Abstract

This study aims to investigate the role of long noncoding RNA RMRP in diabetic peripheral neuropathy (DPN) and its potential mechanisms. We used high glucose (HG) treatment on Schwann cells (SCs) and established a DPN rat model to study the role of RMRP in DPN. RT-qPCR was employed to assess the levels of RMRP and miR-3142. The targeting relationship between RMRP and miR-3142 was verified through dual-luciferase reporter assays, RIP assays, and RNA pull-down experiments. CCK-8 assays and flow cytometry were used to evaluate cell proliferation and apoptosis. The von Frey test and thermal stimulus apparatus measured the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in rats. In addition, the motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the rats were assessed. RMRP was abnormally expressed in both HG-treated SCs and DPN rats. Inhibition of RMRP significantly alleviated the reduction in SCs proliferation and the increase in apoptosis induced by HG, while also reducing oxidative stress and neuroinflammation levels. In DPN rats, inhibition of RMRP improved MWT and TWL and enhanced nerve conduction velocity, whereas inhibition of miR-3142 diminished the protective effects of si-RMRP. Inhibiting RMRP can relieve DPN-related oxidative stress and cell inflammation, as well as reduce pain hypersensitivity and the decline in nerve conduction velocity in rats by upregulating miR-3142.