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Aquaporin Expression in Colonic Mucosal Biopsies From Irritable Bowel Syndrome With Diarrhea.
Clinical and Translational Gastroenterology ( IF 3.6 ) Pub Date : 2019-04-01 , DOI: 10.14309/ctg.0000000000000019
Michael Camilleri 1 , Paula Carlson 1 , Victor Chedid 1 , Priya Vijayvargiya 1 , Duane Burton 1 , Irene Busciglio 1
Affiliation  

INTRODUCTION Aquaporin (AQP) channels are involved in regulating fluid homeostasis in the colon. Several AQP channels were detected in human colon epithelial cells. In a previous study, rats fed 1% (wt/wt) sodium cholate had increased AQP3, 7, and 8 levels, suggesting AQP involvement in bile acid diarrhea (BAD). Our aim was to compare AQP expressions in rectosigmoid mucosal (RSM) biopsies from patients with irritable bowel syndrome-diarrhea (IBS-D) (divided into those with normal or high fecal BA excretion) and in patients with IBS-constipation (IBS-C) compared with healthy controls. METHODS In RSM biopsies from 44 patients with IBS-D (with normal (<) or high (>2,337 μmol/48 hours (BAD)) fecal BA excretion), 10 patients with IBS-C, and 17 healthy controls, we measured expressions of AQP1, 3, 7, and 8, with RT-PCR (housekeeper gene GAPDH). We analyzed RNA for expression by RT-PCR assays, with expression calculated using 2-based fold-change. Comparisons of IBS groups were corrected for false detection rate (Bonferroni correction for 12 comparisons; P < 0.0042). AQP protein measurements on biopsies from 3 healthy controls, 3 patients with IBS-D, and 3 patients with BAD were performed by western blots (GAPDH housekeeping protein). RESULTS In RSM from patients with IBS-D (but not IBS-C), mRNA expression of AQP3 was decreased, and AQP7 and 8 were increased relative to controls. Fold differences were not different in IBS-D with or without BAD. Western blots confirmed increased expression of AQP7 and 8 and decreased AQP3 proteins in biopsies from patients with IBS-D compared with controls. CONCLUSIONS Increased AQP7 and 8 and decreased AQP3 expressions in RSM suggest that further studies on AQPs' potential role in the pathophysiology of diarrhea in IBS-D are warranted.

中文翻译:

腹泻性肠易激综合征结肠粘膜活检中水通道蛋白的表达。

简介 水通道蛋白 (AQP) 通道参与调节结肠中的液体稳态。在人结肠上皮细胞中检测到多个 AQP 通道。在之前的一项研究中,喂食 1%(wt/wt)胆酸钠的大鼠 AQP3、7 和 8 水平升高,表明 AQP 参与胆汁酸腹泻 (BAD)。我们的目的是比较肠易激综合征-腹泻 (IBS-D) 患者(分为粪便 BA 排泄量正常或高的患者)和 IBS 便秘患者 (IBS-C) 直肠乙状结肠粘膜 (RSM) 活检中 AQP 的表达。 )与健康对照相比。方法 在 44 名 IBS-D 患者(粪便 BA 排泄量正常 (<) 或高 (>2,337 μmol/48 小时 (BAD)))、10 名 IBS-C 患者和 17 名健康对照者的 RSM 活检中,我们测量了表达使用 RT-PCR(管家基因 GAPDH)检测 AQP1、3、7 和 8。我们通过 RT-PCR 测定分析了 RNA 的表达,并使用基于 2 的倍数变化计算表达。IBS 组的比较针对错误检测率进行了校正(12 次比较的 Bonferroni 校正;P < 0.0042)。通过蛋白质印迹(GAPDH 管家蛋白)对 3 名健康对照、3 名 IBS-D 患者和 3 名 BAD 患者的活检样本进行 AQP 蛋白测量。结果 在 IBS-D 患者(而非 IBS-C)的 RSM 中,与对照组相比,AQP3 的 mRNA 表达降低,AQP7 和 8 的 mRNA 表达增加。伴有或不伴有 BAD 的 IBS-D 的倍数差异没有差异。蛋白质印迹证实,与对照组相比,IBS-D 患者的活检组织中 AQP7 和 8 的表达增加,AQP3 蛋白的表达减少。结论 RSM 中 AQP7 和 8 表达增加以及 AQP3 表达减少表明,有必要进一步研究 AQP 在 IBS-D 腹泻病理生理学中的潜在作用。
更新日期:2019-11-01
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