USP22 overexpression mitigates spinal cord injury via NLRP3 pathway modulation.

Abstract

INTRODUCTION: The purpose of this study was to explore the effect of ubiquitin-specific protease (USP) 22 overexpression on spinal cord injury (SCI) in rats and its potential mechanism, to assess its role in the recovery of neurological function. MATERIAL AND METHODS: A rat model of SCI was established. The rats were divided into four groups: the Sham group, the SCI group, the SCI + USP22Ad-USP22 group, and the SCI + vector group. The Basso Mouse Scale for locomotion was used for motor function scores. Real-time quantitative polymerase chain reaction and western blot were applied to detect the expression levels of USP22, inducible nitric oxide synthase, cluster of differentiation (CD) 86, arginase 1, and CD206. Additionally, the expression of inflammatory markers and microglial activation were assessed using immunofluorescence and enzyme-linked immunosorbent assay. Furthermore, western blot was employed to measure the expression levels of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway-related proteins. RESULTS: USP22 overexpression significantly improved the motor function of SCI rats, reduced the levels of microglial activation, and inhibited the activation of the nuclear factor-kB pathway. Additionally, USP22 overexpression not only reduced the expression levels of pro-inflammatory mediators (inducible nitric oxide synthase, CD86, tumor necrosis factor a, interleukin (IL)-1b, and IL-6) but also increased the expression levels of anti-inflammatory markers (arginase 1 and CD206). Furthermore, USP22 overexpression inhibited the expression of NLRP3 inflammasome-related proteins, alleviated neuro- inflammatory responses and promoted neurological function recovery. CONCLUSIONS: USP22 overexpression can improve neuroinflammation and motor function in SCI model rats, which may be related to the inhibition of NLRP3 inflammasome pathway activation.