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Stress induces more serious barrier dysfunction in follicle-associated epithelium than villus epithelium involving mast cells and protease-activated receptor-2.

ABSTRACT: 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 vivo and 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 WAS in vivo and CRF in 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.

SUBMITTER: Zhang L

PROVIDER: S-EPMC5503989 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Stress induces more serious barrier dysfunction in follicle-associated epithelium than villus epithelium involving mast cells and protease-activated receptor-2.

Zhang Lei L Song Jun J Bai Tao T Qian Wei W Hou Xiao-Hua XH

Scientific reports 20170710 1

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 U ...[more]

PMID: 28694438

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Project description:Regulation of intestinal epithelial turnover is a key component of villus maintenance in the intestine. The balance of cell turnover can be perturbed by various extrinsic factors including the cytokine TNF, a cell signaling protein that mediates both proliferative and cytotoxic outcomes. Under conditions of infection and damage, defects in autophagy are associated with TNF-mediated cell death and tissue damage in the intestinal epithelium. However, a direct role of autophagy within the context of enterocyte cell death during homeostasis is lacking. Here, we generated mice lacking ATG14 (autophagy related 14) within the intestinal epithelium [Atg14f/f Vil1-Cre (VC)+]. These mice developed spontaneous villus loss and intestinal epithelial cell death within the small intestine. Based on marker studies, the increased cell death in these mice was due to apoptosis. Atg14f/f VC+ intestinal epithelial cells demonstrated sensitivity to TNF-triggered apoptosis. Correspondingly, both TNF blocking antibody and genetic deletion of Tnfrsf1a/Tnfr1 rescued villus loss and cell death phenotype in Atg14f/f VC+ mice. Lastly, we identified a similar pattern of spontaneous villus atrophy and cell death when Rb1cc1/Fip200 was conditionally deleted from the intestinal epithelium (Rb1cc1f/f VC+). Overall, these findings are consistent with the hypothesis that factors that control entry into the autophagy pathway are also required during homeostasis to prevent TNF triggered death in the intestine. Abbreviations: ANOVA: analysis of variance; Atg14: autophagy related 14; Atg16l1: autophagy related 16-like 1 (S. cerevisiae); Atg5: autophagy related 5; cCASP3: cleaved CASP3/caspase-3; cCASP8: cleaved CASP8/caspase-8; CHX: cycloheximide; EdU: 5-ethynyl-2´-deoxyuridine thymidine; f/f: flox/flox; H&E: hematoxylin and eosin; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Nec-1: necrostatin-1; Rb1cc1/Fip200: RB1-inducible coiled-coil 1; Ripk1: receptor (TNFRSF)-interacting serine-threonine kinase 1; Ripk3: receptor (TNFRSF)-interacting serine-threonine kinase 3; Tnfrsf1a/Tnfr1: tumor necrosis factor receptor superfamily, member 1a; Tnf/ Tnfsf1a: tumor necrosis factor; VC: Vil1/villin 1-Cre.

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Dataset Information

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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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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