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.

中文翻译：

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lncRNA MEG3通过上调Nrf2抑制p38/NF-κB通路减轻大鼠间质性膀胱炎

目的

间质性膀胱炎(interstitial cystitis, IC)是一种以尿频、尿急、膀胱或盆底疼痛为特征的慢性疼痛综合征，严重影响患者的生活质量。本研究旨在探讨长链非编码 RNA Maternally Expressed Gene3 (lncRNA MEG3) 在 IC 中的作用和机制。

方法

通过腹腔注射环磷酰胺联合膀胱灌注非瑟酮和肿瘤坏死因子-α（TNF-α）模拟IC建立IC大鼠模型。使用TNF-α诱导的大鼠膀胱上皮细胞建立体外模型。H&E 染色用于评估膀胱组织损伤，ELISA 用于测量炎性细胞因子水平。蛋白质印迹分析用于检测 Nrf2、Bax、Bcl-2、cleaved caspase-3、p-p38、p38、p-NF-κB 和 NF-κB 蛋白表达水平。RNA 免疫沉淀和 RNA pull-down 测定用于检查 MEG3 和 Nrf2 之间的相互作用。

结果

MEG3 水平在 IC 组织和膀胱上皮细胞中上调，而 Nrf2 表达被发现下调。MEG3 的敲低减少了膀胱组织损伤、炎症、氧化应激和细胞凋亡。MEG3 与 Nrf2 呈负相关。MEG3 的下调通过上调 Nrf2 和抑制 p38/NF-κB 通路来减轻 IC 炎症和损伤。

结论

MEG3 的下调通过上调 Nrf2 和抑制 p38/NF-κB 通路减轻 IC 大鼠的炎症和损伤。