LncRNA MEG3 alleviates interstitial cystitis in rats by upregulating Nrf2 and inhibiting the p38/NF-κB pathway. (May 2023)

• Record Type: Journal Article
• Authors: Wang, Min; Li, Xudong; Yang, Zengyue; Chen, Yong; Shu, Tao; Huang, Yi
• Is Part Of: Cytokine. Volume 165(2023)
• Publication Date: 2023-05
• Subjects: Interstitial cystitis -- Maternally Expressed Gene3 -- Nrf2 -- p38/NF-κB pathway -- Inflammation; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2023.156169
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: MEG3 levels are upregulated in IC. MEG3 is negatively correlated with Nrf2 in IC. Downregulation of MEG3 alleviates IC via the Nrf2/p38/ NF-κB pathway. Abstract: Purpose: Interstitial cystitis (IC), a chronic pain syndrome characterized by urinary frequency, urgency, and bladder or pelvic floor pain, severely affects the quality of life of patients. The aim of this study was to investigate the role and mechanism of long noncoding RNA Maternally Expressed Gene3 (lncRNA MEG3) in IC. Methods: An IC rat model was established by intraperitoneal injection of cyclophosphamide combined with bladder perfusion of fisetin and tumor necrosis factor-α (TNF-α) to mimic IC. An in vitro model was established using TNF-α-induced rat bladder epithelium cells. H&E staining was used to assess bladder tissue damage and ELISA was used to measure inflammatory cytokine levels. Western blot analysis was used to examine Nrf2, Bax, Bcl-2, cleaved caspase-3, p-p38, p38, p-NF-κB and NF-κB protein expression levels. RNA immunoprecipitation and RNA pull-down assays were used to examine the interaction between MEG3 and Nrf2. Results: MEG3 levels were upregulated in IC tissues and bladder epithelial cells, whereas Nrf2 expression was found to be downregulated. Knockdown of MEG3 reduced bladder tissue injury, inflammation, oxidative stress and apoptosis. MEG3 was negatively correlated with Nrf2. Downregulation of MEG3 alleviated IC inflammation and injury by upregulating Nrf2 and inhibiting the p38/NF-κB pathway. Conclusion: Downregulation of MEG3 alleviated inflammation and injury in IC rats by upregulating Nrf2 and inhibiting the p38/NF-κB pathway.