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Modulation of Intestinal Epithelial Permeability via Protease-Activated Receptor-2-Induced Autophagy
Protease-activated receptor 2 (PAR2) alleviates intestinal inflammation by upregulating autophagy. PAR2 also modulates tight junctions through β-arrestin signaling. Therefore, we investigated the effect of PAR2-induced autophagy on intestinal epithelial tight junctions and permeability. RT-PCR, West...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909592/ https://www.ncbi.nlm.nih.gov/pubmed/35269499 http://dx.doi.org/10.3390/cells11050878 |
Sumario: | Protease-activated receptor 2 (PAR2) alleviates intestinal inflammation by upregulating autophagy. PAR2 also modulates tight junctions through β-arrestin signaling. Therefore, we investigated the effect of PAR2-induced autophagy on intestinal epithelial tight junctions and permeability. RT-PCR, Western blot analysis, and immunoprecipitation were performed to investigate the underlying molecular mechanisms by which PAR2 regulates autophagy and intestinal epithelial tight junctions. Inhibition of PAR2 by GB83, a PAR2 antagonist, decreased the expression of autophagy-related and tight-junction-related factors in Caco-2 cells. Moreover, inhibition of PAR2 decreased intestinal transepithelial electrical resistance. When PAR2 was activated, intestinal permeability was maintained, but when autophagy was suppressed by chloroquine, intestinal permeability was significantly increased. In addition, the prolongation of ERK1/2 phosphorylation by PAR2–ERK1/2–β-arrestin assembly was reduced under autophagy inhibition conditions. Therefore, PAR2 induces autophagy to regulate intestinal epithelial permeability, suggesting that it is related to the β-arrestin–ERK1/2 pathway. In conclusion, regulating intestinal epithelial permeability through PAR2-induced autophagy can help maintain mucosal barrier integrity. Therefore, these findings suggest that the regulation of PAR2 can be a suitable strategy to treat intestinal diseases caused by permeability dysfunction. |
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