Division of Gastroenterology, Union Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, China.
Division of Urology, Union Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, China.
Dig Liver Dis. 2018 Nov;50(11):1195-1204. doi: 10.1016/j.dld.2018.04.016. Epub 2018 Apr 27.
Defects in mucus and intestinal epithelia can lead to intestinal inflammation in colitis. Reduced peroxisome proliferator-activated receptor gamma (PPAR) in the mucosa may contribute to inflammation. However, the roles of PPAR in the intestinal barrier remain poorly understood.
Chronic colitis was induced in C57BL/6 mice by administration of dextran sulfate sodium (DSS) for 27 days. Three days before DSS treatment, mice were treated with the PPAR agonist rosiglitazone (Ro) orally at 20 mg kg day.
The colitis based on disease activity index and colonic histopathology was significantly ameliorated in the DSS + Ro group. Additionally, mice in the DSS + Ro group had a thicker mucous layer than those in DSS + NS group, and muc2 mRNA expression was elevated significantly along with the mouse atonal homolog, SAM-pointed domain-containing Ets-like factor, and anterior gradient 2 genes. Moreover, tight junctions were up-regulated, whereas long myosin light chain kinase and phosphorylation of the myosin II light chain were lower in DSS + Ro mice. Similarly, after HT-29 and Caco-2 cells were treated by LPS or LPS + Ro, PPAR activation by Ro could effectively improve the intestinal barrier, including intestinal mucus and tight junctions.
Our results demonstrate that activated PPAR could effectively promote intestinal mucus integrity by increasing the number of goblet cells, the glycosylation of mucins, and tight junctions via an MLCK-dependent mechanism.
黏液和肠上皮缺陷可导致结肠炎中的肠道炎症。黏膜中过氧化物酶体增殖物激活受体 γ（PPAR）减少可能导致炎症。然而，PPAR 在肠道屏障中的作用仍知之甚少。
通过给予葡聚糖硫酸钠（DSS）27 天，在 C57BL/6 小鼠中诱导慢性结肠炎。在 DSS 处理前 3 天，用 PPAR 激动剂罗格列酮（Ro）经口以 20mg/kg/天的剂量对小鼠进行处理。
基于疾病活动指数和结肠组织病理学的结肠炎在 DSS+Ro 组中得到明显改善。此外，DSS+Ro 组的小鼠比 DSS+NS 组的小鼠具有更厚的黏液层，并且 muc2 mRNA 表达显著升高，同时伴随着 atonal 同源物、SAM 点结构域包含 Ets 样因子和前梯度 2 基因。此外，紧密连接上调，而长肌球蛋白轻链激酶和肌球蛋白 II 轻链的磷酸化水平在 DSS+Ro 小鼠中较低。同样，在 HT-29 和 Caco-2 细胞用 LPS 或 LPS+Ro 处理后，Ro 对 PPAR 的激活可以通过肌球蛋白轻链激酶依赖性机制有效改善肠道屏障，包括肠道黏液和紧密连接。
我们的结果表明，激活的 PPAR 可以通过增加杯状细胞的数量、黏蛋白的糖基化和紧密连接来有效促进肠道黏液完整性。
