Lameris Anke L, Huybers Sylvie, Kaukinen Katri, Mäkelä Tuula H, Bindels René J, Hoenderop Joost G, Nevalainen Pasi I
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre , The Netherlands.
Scand J Gastroenterol. 2013 Jan;48(1):58-69. doi: 10.3109/00365521.2012.741616. Epub 2012 Dec 3.
Claudins, being part of the tight junction protein family, partially determine the integrity and paracellular permeability of the intestinal epithelium. The aim of this study was twofold. First, the authors set out to create an overview of claudin mRNA expression along the proximal-distal axis of the healthy human intestine. Second, the authors aimed to analyze expression levels of claudins in patients with active and inactive inflammatory bowel diseases (IBD) such as Crohn's disease or ulcerative colitis (UC).
mRNA expression levels of claudins were determined in gastrointestinal biopsies from healthy patients as well as patients diagnosed with IBD using SybrGreen real-time PCR.
Claudins show distinct expression patterns throughout the gastrointestinal tract. Some claudins show a proximal expression pattern, such as CLDN18 which is solely expressed in the stomach, and CLDN2 and -15 that are predominantly expressed in the proximal parts of the gastrointestinal tract. Other claudins, such as CLDN3, -4, -7 and -8, are predominantly expressed in the distal parts of the gastrointestinal tract or show a ubiquitous expression pattern throughout the entire gastrointestinal tract, which is the case for CLDN12. In addition, we show that changes in claudin expression in IBD are dependent on gastrointestinal location and inflammatory activity.
This study provides detailed mRNA expression patterns of various claudins throughout the human gastrointestinal tract. Analysis of expression levels of claudins in patients with CD, active and inactive UC shows that changes in expression are confined to specific intestinal segments and strongly depend on inflammatory activity.
紧密连接蛋白家族的成员紧密连接蛋白部分决定了肠上皮的完整性和细胞旁通透性。本研究有两个目的。首先,作者着手概述紧密连接蛋白mRNA在健康人肠道近端至远端轴上的表达情况。其次,作者旨在分析患有活动性和非活动性炎症性肠病(IBD)如克罗恩病或溃疡性结肠炎(UC)患者中紧密连接蛋白的表达水平。
使用SybrGreen实时PCR测定健康患者以及诊断为IBD患者的胃肠道活检组织中紧密连接蛋白的mRNA表达水平。
紧密连接蛋白在整个胃肠道呈现出不同的表达模式。一些紧密连接蛋白呈现近端表达模式,如仅在胃中表达的CLDN18,以及主要在胃肠道近端表达的CLDN2和CLDN15。其他紧密连接蛋白,如CLDN3、CLDN4、CLDN7和CLDN8,主要在胃肠道远端表达或在整个胃肠道呈现普遍表达模式,CLDN12就是这种情况。此外,我们表明IBD中紧密连接蛋白表达的变化取决于胃肠道位置和炎症活动。
本研究提供了各种紧密连接蛋白在整个人胃肠道中的详细mRNA表达模式。对克罗恩病、活动性和非活动性溃疡性结肠炎患者中紧密连接蛋白表达水平的分析表明,表达变化局限于特定肠段,并且强烈依赖于炎症活动。