Department of Urology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China.
Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
J Cell Biochem. 2020 Feb;121(2):1227-1237. doi: 10.1002/jcb.29356. Epub 2019 Oct 8.
Toll-like receptor-7 (TLR7) is functionally involved in the pathogenesis of Hunner-type interstitial cystitis (HIC). In addition, maternally expressed gene 3 (MEG3) is implicated in many urethral diseases. In this study, we aimed to verify the hypothesis that exosomal MEG3 in urine can be used as a novel diagnostic biomarker for HIC.
Electron microscopy was utilized to observe the distribution of urinary exosomes between the case group and the control group. Receiver operating characteristic analysis was utilized to compare the diagnostic values of MEG3 and miR-19a-3p. Computational analysis and luciferase assay were conducted to identify the correlation between MEG3 and miR-19a-3p as well as between TLR7 and miR-19a-3p. In addition, real-time polymerase chain reaction and Western blot were performed to establish the signaling pathways implicated in the pathogenesis of HIC.
When age and gender distributions are excluded, urinary exosomes were equally distributed between case and control groups. The area under the curve of MEG3 was larger than that of miR-19a-3p, indicating that MEG3 has a better value in the diagnosis of HIC. In addition, patients with HIC showed elevated MEG3 expression and inhibited miR-19a-3p expression, thus establishing a negative correlation between MEG3 and miR-19a-3p. MEG3 and TLR7 were both identified as targets of miR-19a-3p, establishing a MEG3/miR-19a-3p/TLR7 signaling pathway, in which MEG3 enhances the expression of TLR7 via inhibiting the expression of miR-19a-3p.
MEG3 level was upregulated in patients with HIC. In addition, MEG3 downregulated miR-19a-3p expression while upregulating TLR7 expression. Furthermore, MEG3 contributes to the pathogenesis of HIC. Therefore, exosomal MEG3 in urine can be used as a biomarker for HIC diagnosis.
Toll 样受体-7（TLR7）在 Hunner 型间质性膀胱炎（HIC）的发病机制中具有功能作用。此外，母系表达基因 3（MEG3）与许多尿道疾病有关。在这项研究中，我们旨在验证这样一个假设，即尿液中的外泌体 MEG3 可用作 HIC 的新型诊断生物标志物。
利用电子显微镜观察病例组和对照组之间尿液中外泌体的分布。利用受试者工作特征分析比较 MEG3 和 miR-19a-3p 的诊断价值。通过计算分析和荧光素酶测定来确定 MEG3 与 miR-19a-3p 以及 TLR7 与 miR-19a-3p 之间的相关性。此外，还进行了实时聚合酶链反应和 Western blot 以建立与 HIC 发病机制相关的信号通路。
当排除年龄和性别分布时，病例组和对照组之间的尿液外泌体分布均匀。MEG3 的曲线下面积大于 miR-19a-3p，表明 MEG3 在 HIC 的诊断中有更好的价值。此外，HIC 患者表现出 MEG3 表达升高和 miR-19a-3p 表达抑制，从而建立了 MEG3 与 miR-19a-3p 之间的负相关关系。MEG3 和 TLR7 均被鉴定为 miR-19a-3p 的靶标，建立了 MEG3/miR-19a-3p/TLR7 信号通路，其中 MEG3 通过抑制 miR-19a-3p 的表达来增强 TLR7 的表达。
HIC 患者的 MEG3 水平升高。此外，MEG3 下调 miR-19a-3p 的表达，同时上调 TLR7 的表达。此外，MEG3 有助于 HIC 的发病机制。因此，尿液中的外泌体 MEG3 可用作 HIC 诊断的生物标志物。
