Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
J Gastroenterol Hepatol. 2021 Apr;36(4):951-958. doi: 10.1111/jgh.15225. Epub 2020 Sep 3.
BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, and bile acids are thought to be associated with the pathogenesis of IBS. Bile acid receptors are expressed on intestinal epithelial cells. However, no study has assessed bile acid receptor proteins in IBS. Therefore, we examined the intestinal mucosal expression of bile acid receptors in patients with IBS. METHODS: Intestinal biopsies were performed in patients with IBS and controls. Mast cells, vitamin D receptor (VDR), and somatostatin were stained with specific antibodies. Levels of VDR, farnesoid X receptor (FXR), takeda-G-protein-receptor-5 (TGR5), claudins, and transient-receptor-potential-cation-channel-subfamily-V-member 6 (TRPV6) were assessed by western blotting. RESULTS: 3Mast cell counts in the second part of the duodenum were significantly higher in patients with IBS than in controls. VDR protein levels were significantly elevated in the duodenum and terminal ileum of patients with IBS compared with controls, although this difference was not seen in the cecum or rectum. FXR and TGR5 protein levels did not differ in any part of the intestine. VDR-positive cryptal epithelia in IBS were distributed not only at basal crypt but also along the upper part of the basal crypt epithelial cells. In contrast, the pattern of gut somatostatin-positive cells, claudins, and TRPV6 levels did not differ. CONCLUSIONS: The number of mast cells in the duodenum was significantly increased, and the protein expression levels of VDR, but not those of FXR or TGR5, were elevated in the duodenal epithelial crypt in patients with IBS.
背景与目的:肠易激综合征(IBS)是最常见的功能性胃肠疾病之一,胆汁酸被认为与 IBS 的发病机制有关。胆汁酸受体在肠上皮细胞上表达。然而,目前尚无研究评估 IBS 患者的胆汁酸受体蛋白。因此,我们检测了 IBS 患者的肠黏膜胆汁酸受体表达。
方法:对 IBS 患者和对照者进行肠活检。用特异性抗体对肥大细胞、维生素 D 受体(VDR)和生长抑素进行染色。采用 Western blot 检测 VDR、法尼醇 X 受体(FXR)、Takeda-G 蛋白受体 5(TGR5)、紧密连接蛋白和瞬时受体电位阳离子通道亚家族 V 成员 6(TRPV6)的水平。
结果:十二指肠第二段肥大细胞计数在 IBS 患者中明显高于对照组。与对照组相比,IBS 患者的十二指肠和回肠 VDR 蛋白水平明显升高,但在盲肠和直肠未见差异。FXR 和 TGR5 蛋白水平在肠道任何部位均无差异。IBS 患者的 VDR 阳性隐窝上皮不仅分布在基底部,也分布在上部基底部上皮细胞。相比之下,肠道生长抑素阳性细胞、紧密连接蛋白和 TRPV6 水平的模式没有差异。
结论:十二指肠肥大细胞数量明显增加,IBS 患者十二指肠上皮隐窝的 VDR 蛋白表达水平升高,但 FXR 或 TGR5 蛋白表达水平没有升高。
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