The MEP1A gene, located on human chromosome 6p (mouse chromosome 17) in a susceptibility region for inflammatory bowel disease (IBD), encodes the alpha-subunit of metalloproteinase meprin A, which is expressed in the intestinal epithelium. This study shows a genetic association of MEP1A with IBD in a cohort of ulcerative colitis (UC) patients. There were four single-nucleotide polymorphisms in the coding region (P=0.0012-0.04), and one in the 3'-untranslated region (P=2 x 10(-7)) that displayed associations with UC. Moreover, meprin-alpha mRNA was decreased in inflamed mucosa of IBD patients. Meprin-alpha knockout mice exhibited a more severe intestinal injury and inflammation than their wild-type counterparts following oral administration of dextran sulfate sodium. Collectively, the data implicate MEP1A as a UC susceptibility gene and indicate that decreased meprin-alpha expression is associated with intestinal inflammation in IBD patients and in a mouse experimental model of IBD.
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机译:MEP1A基因位于人肠炎性疾病(IBD)易感性区域的6p号染色体(小鼠17号染色体)上,它编码金属蛋白酶meprin A的α亚基,该蛋白在肠上皮细胞中表达。这项研究显示了溃疡性结肠炎(UC)患者队列中MEP1A与IBD的遗传关联。在编码区有四个单核苷酸多态性(P = 0.0012-0.04),在3'-非翻译区(P = 2 x 10(-7))有一个单核苷酸多态性,显示与UC的关联。而且,IBD患者发炎的粘膜中的meprin-αmRNA降低。口服葡聚糖硫酸钠后,Meprin-α基因敲除小鼠比野生型小鼠表现出更严重的肠道损伤和炎症。总体而言,该数据暗示MEP1A为UC易感基因,并表明在IBD患者和IBD小鼠实验模型中,降低的meprin-α表达与肠道炎症有关。
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