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Betaine attenuates LPS-induced downregulation of Occludin and Claudin-1 and restores intestinal barrier function
BMC Veterinary Research ( IF 2.3 ) Pub Date : 2020-03-04 , DOI: 10.1186/s12917-020-02298-3
Jingtao Wu 1 , Caimei He 1 , Jie Bu 1 , Yue Luo 1 , Shuyuan Yang 1 , Chengyan Ye 1 , Silei Yu 1 , Binsheng He 2, 3 , Yulong Yin 2, 3 , Xiaoping Yang 1, 2, 3
Affiliation  

The intestinal epithelial barrier, which works as the first line of defense between the luminal environment and the host, once destroyed, it will cause serious inflammation or other intestinal diseases. Tight junctions (TJs) play a vital role to maintain the integrity of the epithelial barrier. Lipopolysaccharide (LPS), one of the most important inflammatory factors will downregulate specific TJ proteins including Occludin and Claudin-1 and impair integrity of the epithelial barrier. Betaine has excellent anti-inflammatory activity but whether betaine has any effect on TJ proteins, particularly on LPS-induced dysfunction of epithelial barriers remains unknown. The purpose of this study is to explore the pharmacological effect of betaine on improving intestinal barrier function represented by TJ proteins. Intestinal porcine epithelial cells (IPEC-J2) were used as an in vitro model. The results demonstrated that betaine enhanced the expression of TJ proteins while LPS (1 μg/mL) downregulates the expression of these proteins. Furthermore, betaine attenuates LPS-induced decreases of TJ proteins both shown by Western blot (WB) and Reverse transcription-polymerase chain reaction (RT-PCR). The immunofluorescent images consistently revealed that LPS induced the disruption of TJ protein Claudin-1 and reduced its expression while betaine could reverse these alterations. Similar protective role of betaine on intestinal barrier function was observed by transepithelial electrical resistance (TEER) approach. In conclusion, our research demonstrated that betaine attenuated LPS-induced downregulation of Occludin and Claudin-1 and restored the intestinal barrier function.

中文翻译:


甜菜碱可减弱 LPS 诱导的 Occludin 和 Claudin-1 下调并恢复肠道屏障功能



肠上皮屏障作为肠腔环境与宿主之间的第一道防线,一旦被破坏,就会引起严重的炎症或其他肠道疾病。紧密连接(TJ)对于维持上皮屏障的完整性起着至关重要的作用。脂多糖 (LPS) 是最重要的炎症因子之一,会下调包括 Occludin 和 Claudin-1 在内的特定 TJ 蛋白,并损害上皮屏障的完整性。甜菜碱具有优异的抗炎活性,但甜菜碱是否对 TJ 蛋白有任何影响,特别是对 LPS 诱导的上皮屏障功能障碍仍不清楚。本研究旨在探讨甜菜碱改善以TJ蛋白为代表的肠道屏障功能的药理作用。使用猪肠上皮细胞(IPEC-J2)作为体外模型。结果表明,甜菜碱增强了 TJ 蛋白的表达,而 LPS (1 μg/mL) 下调了这些蛋白的表达。此外,蛋白质印迹 (WB) 和逆转录聚合酶链反应 (RT-PCR) 均显示,甜菜碱可减弱 LPS 诱导的 TJ 蛋白减少。免疫荧光图像一致表明,LPS 诱导 TJ 蛋白 Claudin-1 的破坏并降低其表达,而甜菜碱可以逆转这些改变。通过跨上皮电阻(TEER)方法观察到甜菜碱对肠屏障功能的类似保护作用。总之,我们的研究表明,甜菜碱可以减弱 LPS 诱导的 Occludin 和 Claudin-1 下调,并恢复肠道屏障功能。
更新日期:2020-04-22
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