Aquaporin expression is downregulated in a murine model of colitis and in patients with ulcerative colitis, Crohn's disease and infectious colitis
Aquaporin expression is downregulated in a murine model of colitis and in patients with ulcerative colitis, Crohn's disease and infectious colitis
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DOI：
10.1007/s00441-004-0932-4
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发表时间：
2004-11-01
影响因子：
3.6
通讯作者：
Beck, PL
中科院分区：
文献类型：
--
作者：
Hardin, JA;Wallace, LE;Beck, PL
结肠炎与电解质和水运输的改变有关。这些变化导致了结肠炎患者经历的一些症状。体液流量的改变也可能增加对粘膜损伤的易感性。最近，在结肠组织中发现了内源性水通道蛋白(Aquaporins，AQPs)。采用逆转录/聚合酶链式反应、Western blotting和免疫组织化学方法检测AQP4、AQP7和AQP8在小鼠结肠炎模型及炎症性肠病和感染性结肠炎中的表达。在C57BL/6小鼠的饮用水中加入2.5%的葡聚糖硫酸钠(DSS)诱发结肠炎。在DSS暴露后12小时至7天和停止DSS暴露后1天至15天的恢复期，对这些小鼠的AQP表达进行了评估。分别于DSS后1天、3天和恢复后7天测定结肠水转运情况。AQP4和AQP8基因的表达在DSS暴露后12~24 h显著降低，并在整个治疗过程中一直处于抑制状态。AQP7的表达变化较大。蛋白质表达模式与观察到的AQP mRNA相似。结肠液分泌的显著改变与AQP亚型表达减少有关。值得注意的是，活动期溃疡性结肠炎、克罗恩氏结肠炎或感染性结肠炎患者的AQP表达也有类似的戏剧性降低，似乎与疾病活动有关。因此，小鼠和人的结肠损伤都与AQP表达下调有关。
Colitis is associated with alterations in electrolyte and water transport. These changes give rise to some of the symptoms experienced by patients with colitis. Alterations in fluid flux may also contribute to increased susceptibility to mucosal injury. Recently, endogenous water channel proteins (aquaporins; AQPs), have been identified in colonic tissue. The expression of AQP4, AQP7 and AQP8 was examined, via reverse transcription/polymerase chain reaction, Western blotting and immunohistochemistry, in a murine model of colitis and in patients with inflammatory bowel disease or infectious colitis. Colitis was induced in C57BL/6 mice by the addition of 2.5% dextran sodium sulphate (DSS) to their drinking water. AQP expression in these mice was assessed following 12 h to 7 days of DSS exposure and during the recovery phase from 1 to 15 days following cessation of DSS exposure. Colonic water transport was measured after 1 and 3 days of DSS and following 7 days of recovery. The expression of AQP4 and AQP8 mRNA was significantly decreased after 12-24 h of DSS exposure and remained depressed throughout the treatment period. Expression of AQP7 was more variable. Protein expression followed a similar pattern to that observed for AQP mRNA. Significant alteration in colonic fluid secretion was correlated with reduced expression of AQP isoforms. Significantly, patients with active ulcerative colonic, Crohn's colitis or infectious colitis had similar dramatic reductions in AQP expression that appeared to be correlated with disease activity. Thus, colonic injury in both mouse and man is associated with a downregulation in AQP expression.