Granlund Atle van Beelen, Beisvag Vidar, Torp Sverre H, Flatberg Arnar, Kleveland Per Martin, Ostvik Ann Elisabeth, Waldum Helge L, Sandvik Arne K
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Scand J Gastroenterol. 2011 Nov;46(11):1316-23. doi: 10.3109/00365521.2011.605463.
To do a genome-wide gene expression study of active and inactive ulcerative colitis and Crohn's disease (inflammatory bowel disease--IBD) and examine the most differentially expressed genes. As the study showed an extreme upregulation of all regenerating islet-derived genes (REG proteins) in active IBD, we further studied the expression of REGs on protein level in active and inactive IBD, as well as in non-IBD (pseudomembranous) colitis.
Microarray analysis was done on a total of 100 pinch biopsy samples from healthy controls and patients with Crohn's disease or ulcerative colitis. Tissue samples from IBD and pseudomembranous colitis were examined with routine histology and immunohistochemical analysis for REGIα, REGIV, DEFA6, and serotonin.
REG mRNAs were up to 83 times overexpressed in diseased mucosa compared with mucosa from healthy individuals. REGIα and REGIV were overexpressed at immunohistochemistry and located to different mucosal cell types. REGIα was expressed in basal half of crypts, REGIV in mid and outer parts of crypts and in surface epithelium and seems to be stored in, and secreted from, goblets. Pseudomembranous colitis samples showed similar staining patterns, and some IBD samples stained REG positive without inflammation on routine histology.
All REG family mRNAs are upregulated in IBD. REGIα and REGIV have different cellular localization, possibly reflecting different biological functions. REG protein expression also in pseudomembranous colitis shows that REG family proteins are regulated in inflammatory injury and repair, not specifically for IBD as previously thought.
对活动期和非活动期溃疡性结肠炎及克罗恩病（炎症性肠病——IBD）进行全基因组基因表达研究，并检测差异最显著的基因。由于该研究显示活动期IBD中所有再生胰岛衍生基因（REG蛋白）均极度上调，我们进一步研究了REG在活动期和非活动期IBD以及非IBD（假膜性）结肠炎患者蛋白质水平的表达情况。
对来自健康对照、克罗恩病或溃疡性结肠炎患者的总共100份钳取活检样本进行微阵列分析。对IBD和假膜性结肠炎的组织样本进行常规组织学检查以及针对REGIα、REGIV、DEFA6和5-羟色胺的免疫组织化学分析。
与健康个体的黏膜相比，病变黏膜中REG mRNA的表达上调高达83倍。REGIα和REGIV在免疫组织化学中表达上调，且定位于不同的黏膜细胞类型。REGIα在隐窝的下半部分表达，REGIV在隐窝的中外部及表面上皮表达，且似乎储存于杯状细胞并从杯状细胞分泌。假膜性结肠炎样本显示出类似的染色模式，一些IBD样本在常规组织学检查中无炎症但REG染色呈阳性。
IBD中所有REG家族mRNA均上调。REGIα和REGIV具有不同的细胞定位，可能反映了不同的生物学功能。假膜性结肠炎中REG蛋白的表达也表明REG家族蛋白在炎症损伤和修复过程中受到调控，并非如之前所认为的那样仅针对IBD。
