Aim. The incidence and clinical manifestations of inflammatory bowel disease (IBD) are thought to have gender differences, which suggests that the estrogen signaling pathway and intestinal flora may play key roles in the pathogenesis of IBD. In IBD, microRNA-155 (miR-155) is upregulated and regulates G protein coupled estrogen receptor (GPER1), which affects the intestinal flora. The objective of this study was to investigate the role of the estrogen receptors and miR-155 in the pathogenesis of IBD. Methods. From July 2018 to July 2019, in the Department of Gastroenterology at Daping Hospital, Army Military Medical University, a total of 50 patients with IBD were included in this study, and 24 healthy examinees were randomly selected as the control group. Colonoscopies were performed, and clinical characteristics and blood samples were collected from all of the subjects. The serum cytokine levels in the patients with IBD and the health donors were detected by ELISA, and the estrogen receptor level measurements for all of the participants were assessed by immunohistochemistry (IHC) and quantitative real-time PCR (qPCR). The miR-155 levels were detected by qPCR in all of the participants, and miR-155^−/− mice were used to investigate the mechanism of miR-155 in the pathogenesis of IBD. Results. The clinical characteristics and medications were different for the IBD patients when gender was considered. The male patients produced more proinflammatory cytokines, and while GPER1 expression was downregulated, miR-155 was upregulated in the patients with IBD. MiR-155 showed proinflammatory activity, while GPER1 showed an anti-inflammatory response during the pathogenesis of IBD. The miR-155^−/− mice showed improvements in weight loss, survival, rectal bleeding, colon length, and histopathological changes compared with the wild-type mice. Furthermore, the male miR-155^−/− mice showed increased inflammation compared to the female miR-155^−/− mice in the above aspects. Conclusion. This study presents evidence indicating that miR-155 plays a key role in the pathogenesis of IBD for the different genders. MiR-155 was upregulated and showed proinflammatory activity, whereas GPER1 showed an anti-inflammatory response during the pathogenesis of IBD. The results demonstrated that more proinflammatory cytokines and reduced GPER1 levels were observed in the male IBD patients. Thus, miR-155 was involved in the regulation of GPER1 and induced gender differences in IBD patients. MiR-155 may be a potential marker for IBD-targeted therapy.

中文翻译：

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MiR-155 介导的 GPER1 失调在与炎症性肠病相关的性别差异中起重要作用

瞄准。炎症性肠病（IBD）的发病率和临床表现存在性别差异，提示雌激素信号通路和肠道菌群可能在IBD的发病机制中起关键作用。在 IBD 中，microRNA-155 (miR-155) 上调并调节影响肠道菌群的G蛋白偶联雌激素受体 (GPER1)。本研究的目的是探讨雌激素受体和 miR-155 在 IBD 发病机制中的作用。方法. 2018年7月至2019年7月，在陆军军医大学大坪医院消化内科，共纳入IBD患者50例，随机选取24例健康受试者作为对照组。进行了结肠镜检查，并从所有受试者中收集了临床特征和血液样本。通过ELISA检测IBD患者和健康捐赠者的血清细胞因子水平，并通过免疫组织化学（IHC）和定量实时PCR（qPCR）评估所有参与者的雌激素受体水平测量值。通过qPCR检测所有参与者的miR-155水平，并使用miR-155 ^-/-小鼠研究miR-155在IBD发病机制中的作用。结果. 当考虑到性别时，IBD患者的临床特征和药物是不同的。男性患者产生更多的促炎细胞因子，而 IBD 患者的 GPER1 表达下调，而 miR-155 上调。MiR-155 表现出促炎活性，而 GPER1 在 IBD 发病过程中表现出抗炎反应。与野生型小鼠相比， miR-155 ^-/-小鼠的体重减轻、存活率、直肠出血、结肠长度和组织病理学变化均有所改善。此外，与雌性miR-155 ^-/-小鼠相比，雄性miR-155 ^-/-小鼠在上述方面表现出增加的炎症。结论. 本研究提供的证据表明 miR-155 在不同性别的 IBD 发病机制中起关键作用。MiR-155 上调并表现出促炎活性，而 GPER1 在 IBD 发病过程中表现出抗炎反应。结果表明，在男性 IBD 患者中观察到更多的促炎细胞因子和降低的 GPER1 水平。因此，miR-155 参与 GPER1 的调节并诱导 IBD 患者的性别差异。MiR-155 可能是 IBD 靶向治疗的潜在标志物。