肠内分泌细胞调节肠道屏障的透性
Jennifer G Nwako1, Sparsh D Patel1, Taevon J Roach1
1Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill School of Medicine, 111 Mason Farm Road, Molecular Biology Research Building 5341C, Chapel Hill, NC 27599.
bioRxiv : the preprint server for biology
|March 31, 2025
概括
肠内分泌细胞对于保持肠壁完整性至关重要. 补充氨酸氨酸 (PYY) 等激素可以恢复屏障功能,为炎症性肠病提供新的治疗途径.
科学领域:
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 由紧密的结节维持的肠上皮屏障,对于营养吸收和病原体防御至关重要.
- 屏障功能障碍和透性增加是炎症性肠病 (IBD) 的标志.
- 目前的治疗方法没有直接向或改善肠道上皮质屏障功能.
研究的目的:
- 研究肠内分泌细胞在维持肠上皮质屏障完整性方面的潜在作用.
- 为了确定肠内分泌细胞是否对于健康的肠道屏障是必要的.
- 探索肠内分泌细胞衍生激素在恢复屏障功能的治疗潜力.
主要方法:
- 已使用的人类肠道体,已被转基因改造以减少肠内分泌细胞的损失.
- 通过穿越性皮质电阻和细胞透性测试来评估屏障功能.
- 评估了关键结点蛋白的局部化和丰富性 (zona-occludens 1,ocludin,claudin-2). 这些蛋白质的位置和丰富性.
- 测试了氨酸氨酸 (PYY) 和氨酸补充剂对屏障功能的影响.
主要成果:
- 肠内分泌细胞对于在干细胞和分化肠内分泌细胞培养中保持屏障完整性至关重要.
- 补充PYY和奥克特雷奥提德可以挽救肠内分泌缺陷肠体中的屏障缺陷.
- 障碍物改善的发生是独立于紧结蛋白水平的显著变化.
- 激素补充在基线和瘤亡因子 (TNF) 诱导的炎症条件下恢复了屏障功能.
结论:
- 肠内分泌细胞在增强肠上皮质屏障功能方面发挥着重要的,以前不被重视的作用.
- 肠内分泌细胞分泌的荷尔蒙,如PYY,可以恢复屏障的完整性.
- 这些发现为改善IBD等炎症性疾病中的肠道屏障功能提供了一种新的治疗策略.
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