miR-191-5p attenuates TNF-α-induced inflammation in nucleus pulposus cells via targeting EGR1

miR-191-5p通过靶向EGR1减弱TNF-α诱导的髓核细胞炎症

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Abstract

BACKGROUND: Intervertebral disc degeneration (IVDD) is an orthopedic degenerative disease characterized by low back pain, the pathogenesis of which remains inadequately understood. Recent research has illuminated a potential link between dysregulation of microRNAs (miRNAs) and the development of IVDD. The study aimed to elucidate the molecular mechanism by which miR-191-5p affects IVDD. METHODS: TNF-α was applied to construct cell models of IVDD. RT-qPCR was utilized to detect the content of miR-191-5p, EGR1 and extracellular matrix (ECM) markers. Dual-luciferase reporter assays were conducted to validate the target relationship. CCK-8 and Transwell assays were employed to measure cell viability and migration rates. ELISA was adopted to detect the concentration of inflammatory factors. RESULTS: The content of miR-191-5p was significantly reduced in the nucleus pulposus (NP) of patients with IVDD. And the higher the degree of the intervertebral disc (IVD) degeneration, the lower the content of miR-191-5p in NP. In vitro, miR-191-5p mimic promoted Collagen II expression while suppressing MMP-13 and MMP-3 expression. This effect was abolished by upregulation of EGR1. Furthermore, overexpression of miR-191-5p promoted cell viability and migration while inhibiting apoptosis and secretion of inflammatory cytokines (IL-1β and IL-18), which was eliminated by upregulated EGR1. CONCLUSION: miR-191-5p enhanced cell viability and migration while concurrently suppressing ECM degradation, apoptosis and inflammatory responses via negative regulation of EGR1, which in turn inhibited the progression of IVDD.

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