Abstract
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.
Highlights
Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn’s disease (CD), result from deregulated inflammation in a genetically susceptible host [1]
We found that miR-155 expression was higher in patients with IBD compared to the control group (p < 0.0001), and miR-155 expression was higher in the male IBD patients compared to the female patients (p < 0.001) (Figure 3(b))
We demonstrated that male patients produce more TNFα, and, we investigated the underlying mechanism of the gender differences observed in patients with IBD
Summary
Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn’s disease (CD), result from deregulated inflammation in a genetically susceptible host [1]. Environmental influences, a disbalance of intestinal microbes, and genetic susceptibility are all involved in the pathophysiology of IBD. E ratio of the incidence of IBD in men and women is 1 : 1.5 [3], but females are 60% less likely to develop inflammation-associated colon cancer compared to males [4]. The activation of GPER1 reduces the production of inflammatory cytokines and increases the production of antiinflammatory cytokines [9, 10], the precise role of GPER1 in the pathogenesis of IBD and its relationship with disease activity is not fully understood. MiR-155 is one of the most highly expressed miRNA in the serum samples of IBD patients, and probiotics improve intestinal inflammation by regulating miR-155 [11]. An miRNA database search revealed that GPER1 is a predicted target of MiR-155
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More From: Canadian Journal of Infectious Diseases and Medical Microbiology
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