Department of Biochemistry, College of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
Departments of Anatomy, College of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
Biomolecules. 2024 Sep 4;14(9):1122. doi: 10.3390/biom14091122.
The pathogenesis of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease is not well understood. This study investigated the roles and regulation of the claudin-1, -2, -3, and -4 isoforms in the pathogenesis of ulcerative colitis, and the potential therapeutic effects of nobiletin.
Colitis was induced in rats by administering dextran sulfate sodium [DSS] in drinking water for seven days. Animals were treated daily with nobiletin [oral, 60 mg/Kg body weight] and studied in four groups, C [non-colitis control], D [DSS-induced colitis], CN [nobiletin-treated non-colitis control], and DN [nobiletin-treated DSS-induced colitis]. On day seven, the animals were sacrificed, and colonic tissues were collected and analyzed.
Both macroscopic and microscopic findings suggest the progression of colitis. In the inflamed colon, claudin-1 and -4 proteins were decreased, claudin-2 increased, while the claudin-3 protein remained unchanged. Except for claudin-1, these changes were not paralleled by mRNA expression, indicating a complex regulatory mechanism. Uniform β-actin expression along with consistent quality and yield of total RNA indicated selectivity of these changes. Nobiletin treatment reversed these changes.
Altered expression of the claudin isoforms -1, -2, and -4 disrupts tight junctions, exposing the lamina propria to microflora, leading to electrolyte disturbance and the development of ulcerative colitis. Nobiletin with its anti-inflammatory properties may be useful in IBD.
溃疡性结肠炎和克罗恩病等炎症性肠病的发病机制尚不清楚。本研究探讨了紧密连接蛋白-1、-2、-3 和 -4 异构体在溃疡性结肠炎发病机制中的作用及其调控，以及诺比汀的潜在治疗作用。
通过在饮用水中添加葡聚糖硫酸钠[DSS]在七天内诱导大鼠结肠炎。动物每天用诺比汀[口服，60mg/Kg 体重]治疗，并分为四组，C[非结肠炎对照]、D[DSS 诱导的结肠炎]、CN[诺比汀治疗的非结肠炎对照]和 DN[诺比汀治疗的 DSS 诱导的结肠炎]。在第 7 天，处死动物，收集结肠组织并进行分析。
宏观和微观观察结果均提示结肠炎的进展。在发炎的结肠中，紧密连接蛋白-1 和 -4 蛋白减少，紧密连接蛋白-2 增加，而紧密连接蛋白-3 蛋白保持不变。除紧密连接蛋白-1 外，这些变化与 mRNA 表达不一致，表明存在复杂的调控机制。β-肌动蛋白表达均匀，总 RNA 的质量和产量一致，表明这些变化具有选择性。诺比汀治疗逆转了这些变化。
紧密连接蛋白异构体-1、-2 和 -4 的表达改变破坏了紧密连接，使固有层暴露于微生物群中，导致电解质紊乱和溃疡性结肠炎的发展。具有抗炎特性的诺比汀可能对 IBD 有用。
