Subepithelial Serotonin Reduces Small Intestinal Epithelial Cell Tightness via Reduction of Occluding Expression
Subepithelial Serotonin Reduces Small Intestinal Epithelial Cell Tightness via Reduction of Occluding Expression
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上皮下5 -羟色胺通过减少闭塞性表达来降低小肠上皮细胞的紧密性
DOI：
10.5152/tjg.2022.20691
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发表时间：
2022-01-01
影响因子：
1.2
通讯作者：
Shiotani, Akiko
中科院分区：
文献类型：
--
作者：
Horie, Hideki;Handa, Osamu;Shiotani, Akiko
背景资料：肠易激综合征（IBS）的确切发病机制尚未解决;然而，最近的研究报告，以大肠杆菌为主的IBS患者表现出小肠通透性增加和含有高5-羟色胺（5-HT;血清素）水平的肠嗜铬细胞数量增加。在这项研究中，我们研究了5 HT是否有潜力调节小肠上皮细胞的通透性，集中在紧密连接相关的proteins.Methods：分化的Caco-2细胞单层的多孔过滤器（Millicell）被使用。然后，将5 HT加入到下Millicell隔室中7天。肠上皮细胞通透性通过测量细胞旁通透性标志物的通量来评估。我们进一步评估了occludin在5 HT刺激的Caco-2 monolumerall.Results的表达：我们发现，5 HT并没有影响Caco-2细胞的活力在浓度高达100 μ M在实验期间。给Caco-2细胞基底侧注射5 HT可增加3 H标记甘露醇（182 Da）的流量，但不增加FITC-葡聚糖（4000 Da）的流量。在紧密连接蛋白中，occludin的表达被特异性地降低，通过用浓度为100 μ M的5 HT刺激。结论：总之，过度的5 HT在基底侧通过减少occludin的表达增加了肠上皮细胞的通透性。
Background: The precise pathogenesis of irritable bowel syndrome (IBS) remains unresolved; however, recent studies have reported that patients with diarrhea-predominant IBS exhibit an increased small intestinal permeability and increased number of enterochromaffin cells containing high 5-hydroxytryptamine (5HT; serotonin) levels. In this study, we investigated whether 5HT has the potential to modulate small intestinal epithelial cell permeability, focusing on tight junction-associated proteins.Methods: The differentiated Caco-2 cell monolayer on porous filters (Millicell) was used. Then, 5HT was added to the lower Millicell compartment for 7 days. Intestinal epithelial cell permeability was assessed by measuring the flux of paracellular permeability markers. We further assessed the expression of occludin in the 5HT-stimulated Caco-2 monolayer.Results: We found that 5HT did not affect the viability of Caco-2 cells at concentrations up to 100 mu M during the experimental period. Administration of 5HT to the basal side of Caco-2 cells increased the flux of 3H-labeled mannitol (182 Da) but did not increase that of FITC-dextran (4000 Da). Among the tight junction proteins, the expression of occludin was specifically decreased by stimulation with 5HT at a concentration of 100 mu M.Conclusion: In conclusion, excessive 5HT in the basal side increased the permeability of intestinal epithelial cells via reduction of occludin expression.