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首页> 外文期刊>The FEBS journal >Effect of n-3 polyunsaturated fatty acids on membrane microdomain localization of tight junction proteins in experimental colitis
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Effect of n-3 polyunsaturated fatty acids on membrane microdomain localization of tight junction proteins in experimental colitis

机译：n-3多不饱和脂肪酸对实验性结肠炎紧密连接蛋白膜微区定位的影响

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摘要

Ulcerative colitis (UC) is a gastrointestinal disorder characterized by an inflammatory process associated with mucosal damage. Many studies have shown that n-3 polyunsaturated fatty acids (PUFAs) possess anti-inflammatory effects in inflammatory bowel disease. The aim of this study was to investigate whether n-3 PUFAs could alleviate intestinal damage in experimental UC. In the present study, we found that in 2,4,6-trinitrobenzenesulfonic acid-induced colitic rats, the damage to the intestinal mucosa was accompanied by a disrupted tight junction (TJ) structure. In accordance with these changes, the distribution and expression of TJ proteins, including occludin, claudin-1, claudin-3, claudin-5, claudin-8 and ZO-1, in membrane microdomains was altered. The distribution of flotillin-1, a lipid raft marker protein, was also changed. Moreover, we found for the first time that n-3 PUFAs prevented redistribution of TJ proteins from Triton X-100-insoluble raft-like membrane microdomains to Triton X-100-soluble fractions. The expression of ZO-1, claudin-1, claudin-5 and claudin-8 was significantly elevated by n-3 PUFAs. n-3 PUFAs also attenuated the disruption of TJ structure and improved the histological score. Our results demonstrate that the expression and distribution of TJ proteins in TJ membrane microdomains might be affected in UC, and that such altered expression of TJ proteins in membrane microdomains in experimental UC is affected by n-3 PUFAs. These findings may have therapeutic potential in intestinal inflammation.
机译：溃疡性结肠炎（UC）是一种胃肠道疾病，其特征在于与黏膜损伤相关的炎症过程。许多研究表明，n-3多不饱和脂肪酸（PUFA）在炎症性肠病中具有抗炎作用。这项研究的目的是调查n-3 PUFA是否可以减轻实验性UC中的肠道损伤。在本研究中，我们发现在2,4,6-三硝基苯磺酸诱导的结肠炎大鼠中，对肠粘膜的损害伴随着紧密连接（TJ）结构的破坏。根据这些变化，TJ蛋白（包括occludin，claudin-1，claudin-3，claudin-5，claudin-8和ZO-1）在膜微区中的分布和表达发生了变化。脂筏标记蛋白flotillin-1的分布也发生了变化。此外，我们首次发现n-3 PUFA阻止TJ蛋白从Triton X-100不溶性筏状膜微结构域向Triton X-100可溶级分的重新分布。 ZO-1，claudin-1，claudin-5和claudin-8的表达被n-3 PUFA显着提高。 n-3 PUFAs还减弱了TJ结构的破坏并改善了组织学评分。我们的结果表明，TJ膜微区中TJ蛋白的表达和分布可能在UC中受到影响，而实验UC中膜微区中TJ蛋白的这种表达变化受到n-3 PUFA的影响。这些发现可能对肠道炎症具有治疗潜力。

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