Stress induces more serious barrier dysfunction in follicle-associated epithelium than villus epithelium involving mast cells and protease-activated receptor-2.
Stress induces more serious barrier dysfunction in follicle-associated epithelium than villus epithelium involving mast cells and protease-activated receptor-2.
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压力会导致毛囊相关上皮比绒毛上皮更严重的屏障功能障碍，涉及肥大细胞和蛋白酶激活受体 2
DOI：
10.1038/s41598-017-05064-y
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发表时间：
2017-07-10
影响因子：
4.6
通讯作者：
Hou XH
中科院分区：
文献类型：
--
作者：
Zhang L;Song J;Bai T;Qian W;Hou XH
心理应激与肠上皮细胞通透性增高有关，这是各种功能性和器质性肠病的基本过程。在本研究中，我们的目的是澄清功能和结构不同的上皮细胞，包括绒毛上皮（VE）和滤泡相关上皮（FAE），一个专门的上皮细胞覆盖的圆顶派尔氏淋巴滤泡的应力诱导的屏障破坏的差异和强调机制。采用Ussing Chamber系统，评估了大鼠体内避水应激（WAS）后和离体暴露于促肾上腺皮质激素释放因子（CRF）的粘膜组织中的上皮通透性。在WAS大鼠和CRF暴露粘膜中观察到结肠、回肠VE和FAE的跨上皮阻力（TER）降低和细胞旁和跨细胞大分子渗透性增加。尤其是FAE组屏障功能障碍更为严重。此外，WAS上调肥大细胞类胰蛋白酶和蛋白酶激活受体2（PAR 2）的表达，这与上皮电导呈正相关。肥大细胞稳定剂克罗埃因钠可明显减轻WAS体内和CRF体外引起的屏障破坏。丝氨酸蛋白酶抑制剂抑肽酶和FUT-175，选择性PAR 2拮抗剂ENMD-1068有效地抑制CRF诱导的FAE高通透性。总之，它得出的结论是，FAE更容易受到压力，肥大细胞和PAR 2信号在这个过程中发挥了关键作用。
Psychological stress has been associated with intestinal epithelial hyperpermeability, the basic process in various functional and organic bowel diseases. In the present study, we aimed to clarify the differences and underlining mechanisms in stress-induced barrier disruption in functionally and structurally distinct epitheliums, including the villus epithelium (VE) and follicle-associated epithelium (FAE), a specialized epithelium overlaid the domes of Peyer’s lymphoid follicles. Employing an Ussing Chamber system, the epithelial permeability was assessed in rats following water avoidance stress (WAS)in vivoand in mucosa tissues exposed to corticotropin-releasing factor (CRF)ex vivo. Decreased transepithelial resistance (TER) and increased paracellular and transcellular macromolecular permeability in colon, ileal VE and FAE had been observed in WAS rats and in CRF-exposed mucosa. Especially, the barrier dysfunction was more serious in the FAE. Moreover, WAS upregulated the expression of mast cell tryptase and protease-activated receptor-2 (PAR2), which positively correlated with epithelial conductance. Mast cell stabilizer cromolyn sodium obviously alleviated the barrier disruption induced by WASin vivoand CRFin vitro. Serine protease inhibitor aprotinin and FUT-175, and selective PAR2 antagonist ENMD-1068 effectively inhibited the CRF-induced FAE hyperpermeability. Altogether, it concluded that the FAE was more susceptible to stress, and the mast cells and PAR2 signaling played crucial roles in this process.
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影响因子：
6
作者：
Bennett, Kaila M.;Parnell, Erinn A.;Lo, David D.
通讯作者：
Lo, David D.
影响因子：
3.5
作者：
Keita, A. V.;Carlsson, A. H.;Soderholm, J. D.
通讯作者：
Soderholm, J. D.
DOI：
10.1007/978-1-4939-0897-4_6
发表时间：
2014-01-01
期刊：
MICROBIAL ENDOCRINOLOGY: THE MICROBIOTA-GUT-BRAIN AXIS IN HEALTH AND DISEASE
影响因子：
--
作者：
Al Omran, Yasser;Aziz, Qasim
通讯作者：
Aziz, Qasim
DOI：
10.1196/annals.1326.028
发表时间：
2006-01-01
期刊：
INFLAMMATORY BOWEL DISEASE: GENETICS, BARRIER FUNCTION, IMMUNOLOGIC MECHANISMS, AND MICROBIAL PATHWAYS
影响因子：
--
作者：
Gullberg, Elisabet;Soderholm, Johan D.
通讯作者：
Soderholm, Johan D.
影响因子：
3.7
作者：
Santos, Javier;Yates, Derrick;Perdue, Mary H.
通讯作者：
Perdue, Mary H.