Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.

中文翻译：

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AQP1 缺乏通过肠道炎症导致邻苯二甲酸盐诱导的上皮屏障破坏


邻苯二甲酸二-2-乙基己酯（DEHP）经常被用作增塑剂，以增强农产品的可塑性和耐久性，但对人类健康和环境造成不利影响。水通道蛋白 1 (AQP1) 是一种主要的水转运通道蛋白，参与维持肠道完整性。然而，DEHP 暴露对肠道健康的影响及其潜在机制仍然难以捉摸。在此，我们确定 DEHP 暴露会导致十二指肠结构受损，并伴有上皮细胞线粒体结构损伤。重要的是，DEHP暴露引起十二指肠炎症上皮细胞损伤和强烈的炎症反应，同时激活TLR4/MyD88/NF-κB信号通路。从机制上讲，DEHP 暴露直接抑制 AQP1 的表达，从而导致炎症反应，最终破坏十二指肠的完整性和屏障功能。总的来说，我们的研究结果揭示了 AQP1 在邻苯二甲酸盐诱导的肠道疾病中的作用，并且 AQP1 可能是治疗肠道疾病或炎症性疾病患者的一种有前途的治疗方法。