Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, 410013, People's Republic of China.
Changsha Medical University, Changsha, 410219, Hunan, People's Republic of China.
BMC Vet Res. 2020 Mar 4;16(1):75. doi: 10.1186/s12917-020-02298-3.
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.
肠道上皮屏障作为腔环境与宿主之间的第一道防线,一旦被破坏,就会导致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,它会下调特定的 TJ 蛋白,包括 Occludin 和 Claudin-1,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,特别是对 LPS 诱导的上皮屏障功能障碍有任何影响尚不清楚。本研究旨在探讨甜菜碱改善 TJ 蛋白为代表的肠道屏障功能的药理作用。猪肠上皮细胞(IPEC-J2)被用作体外模型。
结果表明,甜菜碱增强了 TJ 蛋白的表达,而 LPS(1μg/ml)下调了这些蛋白的表达。此外,甜菜碱通过 Western blot(WB)和逆转录-聚合酶链反应(RT-PCR)均减弱了 LPS 诱导的 TJ 蛋白表达下调。免疫荧光图像一致显示,LPS 诱导 TJ 蛋白 Claudin-1 破坏,并降低其表达,而甜菜碱可逆转这些改变。TEER 方法也观察到甜菜碱对肠道屏障功能的类似保护作用。
总之,我们的研究表明,甜菜碱可减轻 LPS 诱导的 Occludin 和 Claudin-1 下调,并恢复肠道屏障功能。