The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn's Disease but Not Ulcerative Colitis Patients.
The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn's Disease but Not Ulcerative Colitis Patients.
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DOI：
10.3390/pharmaceutics15030811
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发表时间：
2023-03-02
期刊：
影响因子：
5.4
通讯作者：
McCole DF
中科院分区：
文献类型：
--
作者：
Park YS;Kang SB;Marchelletta RR;Penrose HM;Ruiter-Visser R;Jung B;Docherty MJ;Boland BS;Sandborn WJ;McCole DF
前列腺素类似物鲁比前列酮被批准用于治疗以便秘为主的肠易激综合征。在结肠炎动物模型中，鲁比前列酮还能保护肠黏膜屏障功能。本研究的目的是确定鲁比前列酮是否能改善克罗恩病（CD）和溃疡性结肠炎（UC）患者离体结肠活检组织的屏障特性。将来自健康受试者、缓解期的CD和UC患者以及活动期CD患者的乙状结肠活检组织置于尤斯灌流室中。用鲁比前列酮或赋形剂处理组织，以确定其对跨上皮电阻（TER）、异硫氰酸荧光素 - 右旋糖酐4kD（FD4）通透性以及对毛喉素和卡巴胆碱的生电离子转运反应的影响。通过免疫荧光法确定紧密连接蛋白闭合蛋白的定位。鲁比前列酮显著增加了对照组、CD和UC缓解期活检组织的离子转运，但对活动期CD没有作用。鲁比前列酮选择性地改善了CD缓解期和活动期疾病活检组织的TER，但对对照组或UC活检组织没有作用。TER的改善与闭合蛋白的膜定位增加有关。与UC相比，鲁比前列酮选择性地改善了CD患者活检组织的屏障特性，且与离子转运反应无关。这些数据表明鲁比前列酮在改善克罗恩病的黏膜完整性方面具有潜在疗效。
The prostone analog, lubiprostone, is approved to manage constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in animal models of colitis. The aim of this study was to determine if lubiprostone improves barrier properties in isolated colonic biopsies from Crohn’s disease (CD) and ulcerative colitis (UC) patients. Sigmoid colon biopsies from healthy subjects, CD and UC patients in remission, and CD patients with active disease were mounted in Ussing chambers. Tissues were treated with lubiprostone or vehicle to determine the effects on transepithelial electrical resistance (TER), FITC-dextran 4kD (FD4) permeability, and electrogenic ion transport responses to forskolin and carbachol. Localization of the tight junction protein, occludin, was determined by immunofluorescence. Lubiprostone significantly increased ion transport across control, CD and UC remission biopsies but not active CD. Lubiprostone selectively improved TER in both CD remission and active disease biopsies but not in control or UC biopsies. The improved TER was associated with increased membrane localization of occludin. Lubiprostone selectively improved barrier properties of biopsies from CD patients vs. UC and independent of an ion transport response. These data indicate that lubiprostone has potential efficacy in improving mucosal integrity in Crohn’s disease.
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DOI：
10.1124/jpet.114.213991
发表时间：
2014-06-01
影响因子：
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