Wang Min, Li Xudong, Yang Zengyue, Chen Yong, Shu Tao, Huang Yi
Department of Urology, Xi'an International Medical Center Hospital, Xi'an 710100, Shaanxi, China.
Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Cytokine. 2023 May;165:156169. doi: 10.1016/j.cyto.2023.156169. Epub 2023 Mar 16.
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.
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.
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.
Downregulation of MEG3 alleviated inflammation and injury in IC rats by upregulating Nrf2 and inhibiting the p38/NF-κB pathway.
间质性膀胱炎（IC）是一种以尿频、尿急以及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母系表达基因3（lncRNA MEG3）在IC中的作用及机制。
通过腹腔注射环磷酰胺并联合槲皮素和肿瘤坏死因子-α（TNF-α）膀胱灌注建立IC大鼠模型，以模拟IC。使用TNF-α诱导的大鼠膀胱上皮细胞建立体外模型。采用苏木精-伊红（H&E）染色评估膀胱组织损伤，酶联免疫吸附测定（ELISA）检测炎性细胞因子水平。蛋白质免疫印迹分析用于检测核因子E2相关因子2（Nrf2）、凋亡相关蛋白Bax、Bcl-2、裂解的半胱天冬酶-3、磷酸化p38、p38、磷酸化核因子κB（NF-κB）和NF-κB的蛋白表达水平。采用RNA免疫沉淀和RNA下拉实验检测MEG3与Nrf2之间相互作用。
IC组织和膀胱上皮细胞中MEG3水平上调，而Nrf2表达下调。敲低MEG3可减轻膀胱组织损伤、炎症、氧化应激和细胞凋亡。MEG3与Nrf2呈负相关。下调MEG3可通过上调Nrf2并抑制p38/NF-κB通路减轻IC炎症和损伤。
下调MEG3通过上调Nrf2并抑制p38/NF-κB通路减轻IC大鼠的炎症和损伤。
