Intestinal inflammation reduces expression of DRA, a transporter responsible for congenital chloride diarrhea
Intestinal inflammation reduces expression of DRA, a transporter responsible for congenital chloride diarrhea
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DOI：
10.1152/ajpgi.1998.275.6.g1445
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发表时间：
1998-12-01
影响因子：
4.5
通讯作者：
Wu, GD
中科院分区：
文献类型：
--
作者：
Yang, HY;Jiang, W;Wu, GD
肠道炎症状态下腹泻的发病机制是一个多因素的过程，涉及炎症介质对上皮转运功能的影响。在体内以及在肠上皮细胞系中检查了结肠炎症对在先天性氯溢患者中突变的氯-硫酸盐阴离子转运体（在腺瘤中下调）的基因表达的影响。DRA.与对照组相比，HLA-B27/β 2 m转基因大鼠的mRNA表达减少了5 - 7倍。原位杂交显示，正常情况下在结肠的上隐窝和表面上皮中表达的HLA-B27/β 2 m转基因大鼠、自发性结肠炎的白细胞介素-10（IL-10）敲除小鼠和溃疡性结肠炎患者的表面上皮中，HLA-B27/β 2 m转基因大鼠和溃疡性结肠炎患者的HLA-B27/β 2 m转基因小鼠的HLA-B27/IL-10敲除小鼠的HLA-B27/β 2 m转基因小鼠的HLA-B27/IL-10敲除小鼠的HLA-B27/IL免疫组化结果显示，在体内，BMPmRNA的表达反映了蛋白质的表达。IL-1 β在体外通过抑制基因转录而降低了p53 mRNA的表达。转运蛋白基因表达减弱导致的结肠表面上皮细胞转运功能丧失，可能在基因转录水平上受到促炎细胞因子的抑制，可能在结肠炎腹泻的发病机制中发挥作用。
The pathogenesis of diarrhea in intestinal inflammatory states is a multifactorial process involving the effects of inflammatory mediators on epithelial transport function. The effect of colonic inflammation on the gene expression of DRA (downregulated in adenoma), a chloride-sulfate anion transporter that is mutated in patients with congenital chloridorrhea, was examined in vivo as well as in an intestinal epithelial cell line. DRA. mRNA expression was diminished five- to sevenfold in the HLA-B27/beta 2m transgenic rat compared with control. In situ hybridization showed that DRA, which is normally expressed in the upper crypt and surface epithelium of the colon, was dramatically reduced in the surface epithelium of the HLA-B27/beta 2m transgenic rat, the interleukin-10 (IL-10) knockout mouse with spontaneous colitis, and in patients with ulcerative colitis. Immunohistochemistry demonstrated that mRNA expression of DRA reflected that of protein expression in vivo. IL-1 beta reduced DRA mRNA expression in vitro by inhibiting gene transcription. The loss of transport function in the surface epithelium of the colon by attenuation of transporter gene expression, perhaps inhibited at the level of gene transcription by proinflammatory cytokines, may play a role in the pathogenesis of diarrhea in colitis.