New Therapeutic Targets in Ulcerative Colitis: The Importance of Ion Transporters in the Human Colon
New Therapeutic Targets in Ulcerative Colitis: The Importance of Ion Transporters in the Human Colon
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DOI：
10.1002/ibd.21432
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发表时间：
2011-04-01
影响因子：
4.9
通讯作者：
Hegyi, Peter
中科院分区：
文献类型：
--
作者：
Farkas, Klaudia;Yeruva, Sunil;Hegyi, Peter
背景资料：水和离子（特别是Na+和Cl-）的吸收是结肠上皮细胞在生理和病理生理条件下的重要功能。尽管全面的动物研究，只有稀缺的可用数据的正常和发炎的人类colon.Methods：在这项研究中，128名健康对照和69例患有溃疡性结肠炎（UC）的离子转运蛋白的活动。我们使用显微荧光测定法、膜片钳和实时逆转录聚合酶链反应（RT-PCR）技术研究了Na+/H+交换器（NHE）1-3、上皮钠通道（ENaC）和SLC 26 A3 Cl-/HCO 3-交换器在从人类活检和手术样本中分离的原发性结肠隐窝中的腺瘤（腺瘤）中下调的表达和功能特征。从结肠隐窝收集的数据显示，在近端和远端结肠中，电中性（通过NHE 3）和生电Na+吸收（通过ENaC）的活性彼此成反比。我们发现NHE 2在结肠的不同部分的活性没有显着差异。表面细胞Cl-/HCO 3-交换在结肠的远端部分更活跃。重要的是，钠和氯离子的吸收在UC中受损，而NHE 1，这已被证明是促进免疫应答，上调了6倍。结论：这些结果开辟了新的治疗靶点在UC。
Background: The absorption of water and ions (especially Na+ and Cl-) is an important function of colonic epithelial cells in both physiological and pathophysiological conditions. Despite the comprehensive animal studies, there are only scarce available data on the ion transporter activities of the normal and inflamed human colon.Methods: In this study, 128 healthy controls and 69 patients suffering from ulcerative colitis (UC) were involved. We investigated the expressional and functional characteristics of the Na+/H+ exchangers (NHE) 1-3, the epithelial sodium channel (ENaC), and the SLC26A3 Cl-/HCO3- exchanger downregulated in adenoma (DRA) in primary colonic crypts isolated from human biopsy and surgical samples using microfluorometry, patch clamp, and real-time reverse-transcription polymerase chain reaction (RT-PCR) techniques.Results: Data collected from colonic crypts showed that the activities of electroneutral (via NHE3) and the electrogenic Na+ absorption (via ENaC) are in inverse ratio to each other in the proximal and distal colon. We found no significant differences in the activity of NHE2 in different segments of the colon. Surface cell Cl-/HCO3- exchange is more active in the distal part of the colon. Importantly, both sodium and chloride absorptions are damaged in UC, whereas NHE1, which has been shown to promote immune response, is upregulated by 6-fold.Conclusions: These results open up new therapeutic targets in UC.