1. USP7 alleviates neuronal inflammation and apoptosis in spinal cord injury via deubiquitinating NRF1/KLF7 axis.
- Author
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Xu Q, Kong F, Zhao G, Jin J, Feng S, and Li M
- Subjects
- Animals, Rats, PC12 Cells, Inflammation metabolism, Male, Neurons metabolism, Neurons drug effects, Ubiquitination drug effects, Lipopolysaccharides pharmacology, Spinal Cord Injuries metabolism, Spinal Cord Injuries pathology, Apoptosis physiology, Apoptosis drug effects, Ubiquitin-Specific Peptidase 7 metabolism, Kruppel-Like Transcription Factors metabolism, Kruppel-Like Transcription Factors genetics, Rats, Sprague-Dawley, Nuclear Respiratory Factor 1 metabolism
- Abstract
Background: Ubiquitin-specific protease 7 (USP7) has been found to be associated with motor function recovery after spinal cord injury (SCI). Therefore, its role and mechanism in SCI process need further exploration., Methods: SCI rat models were established via performing laminectomy at the T9-T11 spinal vertebrae and cutting spinal cord tissues. SCI cell models were constructed by inducing PC12 cells with lipopolysaccharide (LPS). The protein levels of USP7, nuclear respiratory factor 1 (NRF1), Krüppel-like factor 7 (KLF7) and apoptosis-related markers were detected by western blot. Cell viability and apoptosis were tested by cell counting kit-8 assay and flow cytometry. The contents of inflammatory factors were examined using ELISA. The interaction between NRF1 and USP7 or KLF7 was analyzed by co-immunoprecipitation assay, chromatin immunoprecipitation assay and dual-luciferase reporter assay, respectively., Results: USP7 was downregulated in SCI rat models and LPS-induced PC12 cells. Overexpressed USP7 promoted viability, while repressed apoptosis and inflammation in LPS-induced PC12 cells. USP7 could stabilize NRF1 protein expression via deubiquitination, and NRF1 knockdown reversed the protective effect of USP7 against LPS-induced PC12 cell injury. NRF1 is bound to KLF7 promoter to enhance its transcription. NRF1 overexpression inhibited LPS-induced PC12 cell inflammation and apoptosis via increasing KLF7 expression., Conclusion: USP7 alleviated inflammation and apoptosis in LPS-induced PC12 cells via NRF1/KLF7 axis, indicating that targeting of USP7/NRF1/KLF7 axis might be a promising treatment strategy for SCI.
- Published
- 2024
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