Altered expression and localization of ion transporters contribute to diarrhea in mice with Salmonella-induced enteritis.
Altered expression and localization of ion transporters contribute to diarrhea in mice with Salmonella-induced enteritis.
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DOI：
10.1053/j.gastro.2013.08.054
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发表时间：
2013-12
期刊：
影响因子：
29.4
通讯作者：
Barrett KE
中科院分区：
文献类型：
--
作者：
Marchelletta RR;Gareau MG;McCole DF;Okamoto S;Roel E;Klinkenberg R;Guiney DG;Fierer J;Barrett KE
肠道沙门氏菌鼠伤寒血清型是一种肠道病原体，它在健康个体中引起自限性腹泻，但对易感人群构成重大健康威胁。由于缺乏合适的小鼠模型，我们对沙门氏菌诱导腹泻的发病机制的理解受到了阻碍。在口服一定剂量的卡那霉素后，感染沙门氏菌的同源BALB/c.D2NrampG169小鼠（携带野生型Nramp1基因）出现明显的腹泻症状。我们利用该模型来阐明沙门氏菌诱导腹泻的病理生理学。
BALB/c.D2NrampG169小鼠先用卡那霉素处理，然后通过口服灌胃感染野生型或突变型沙门氏菌。分离结肠组织，并使用尤斯灌流室、定量聚合酶链反应、免疫印迹和共聚焦显微镜分析来研究离子转运蛋白的功能和表达以及细胞增殖情况。
尤斯灌流室研究表明，感染的结肠组织中基础的和/或腺苷3′,5′ - 环磷酸介导的电离子转运减少，这归因于氯离子或钠离子转运的变化，具体取决于所研究的肠段。感染的影响至少部分是由细菌的沙门氏菌致病岛1和沙门氏菌致病岛2编码的毒力系统所分泌的效应蛋白介导的。感染组织显示表面结肠上皮细胞中腺瘤下调的氯 - 碳酸氢盐交换体表达降低。囊性纤维化跨膜传导调节因子在结肠隐窝上皮细胞中发生内化，但总体表达水平没有变化。共聚焦分析、光密度测定和定量聚合酶链反应显示，在感染沙门氏菌的小鼠远端结肠中上皮钠通道β的表达降低。转运蛋白表达、定位和/或功能的变化伴随着感染沙门氏菌的小鼠隐窝增生。
沙门氏菌感染通过改变介导结肠水吸收的转运蛋白的表达和/或功能而诱导腹泻，这可能反映了这样一个事实：当感染使增殖率增加时，上皮细胞分化为表面细胞的时间减少。
Salmonella enterica serovar Typhimurium is an enteropathogen that causes self-limiting diarrhea in healthy individuals, but poses a significant health threat to vulnerable populations. Our understanding of the pathogenesis of Salmonella-induced diarrhea has been hampered by the lack of a suitable mouse model. After a dose of oral kanamycin, Salmonella-infected congenic BALB/c.D2NrampG169 mice, which carry a wild-type Nramp1 gene, develop clear manifestations of diarrhea. We used this model to elucidate the pathophysiology of Salmonella-induced diarrhea. BALB /c.D2NrampG169 mice were treated with kanamycin and then infected with wild-type or mutant Salmonella by oral gavage. Colon tissues were isolated and Ussing chambers, quantitative polymerase chain reaction, immunoblot, and confocal microscopy analyses were used to study function and expression of ion transporters and cell proliferation. Studies with Ussing chambers demonstrated reduced basal and/or adenosine 3′,5′-cyclic monophosphate–mediated electrogenic ion transport in infected colonic tissues, attributable to changes in chloride or sodium transport, depending on the segment studied. The effects of infection were mediated, at least in part, by effector proteins secreted by the bacterial Salmonella pathogenicity island 1– and Salmonella pathogenicity island-2–encoded virulence systems. Infected tissue showed reduced expression of the chloride–bicarbonate exchanger down-regulated in adenoma in surface colonic epithelial cells. Cystic fibrosis transmembrane conductance regulator was internalized in colonic crypt epithelial cells without a change in overall expression levels. Confocal analyses, densitometry, and quantitative polymerase chain reaction revealed that expression of epithelial sodium channel β was reduced in distal colons of Salmonella-infected mice. The changes in transporter expression, localization, and/or function were accompanied by crypt hyperplasia in Salmonella-infected mice. Salmonella infection induces diarrhea by altering expression and/or function of transporters that mediate water absorption in the colon, likely reflecting the fact that epithelial cells have less time to differentiate into surface cells when proliferation rates are increased by infection.
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影响因子：
2.9
作者：
Lamprecht, G;Heil, A;Seidler, U
通讯作者：
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