期刊
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
卷 58, 期 5, 页码 460-470出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/00365521.2022.2141075
关键词
Functional dyspepsia; duodenum; mast cells; transepithelial electrical resistance; tight junction proteins
This study found that changes in intestinal barrier and tight junction proteins may be associated with the occurrence and development of functional dyspepsia (FD). Mast cells may play a crucial role in the development of FD by disrupting duodenal barrier function through modulating the levels of tight junction proteins. The PAR-2 and ERK1/2 signaling pathways may mediate the pathogenesis of FD.
Background Functional dyspepsia (FD) is a common functional gastrointestinal (GI) disorder, but its pathophysiology is poorly understood. Mast cells (MCs) may play a critical role in the development of FD. Therefore, the aim of this study was to investigate the effect of MCs on barrier function, tight junction (TJ) proteins and related signaling pathways. Methods The expression of the TJ proteins claudin-8, ZO-1 and occludin in biopsy tissues from seven FD patients and five controls was assessed. Based on the in vivo results, we further investigated the effect of (1) MC degranulation in a coculture model of Caco-2/RBL-2H3 cells and tryptase in Caco-2 monolayers, (2) MC degranulation in the presence or absence of a PAR-2 antagonist and (3) MC degranulation in the presence or absence of an ERK1/2 signaling pathway inhibitor. The epithelial integrity of Caco-2 cell monolayers was assessed by measuring the transepithelial electrical resistance (TEER). The expression of TJ proteins was evaluated by western blotting, QT-PCR and immunostaining. Results Epithelial claudin-8, ZO-1 and occludin protein expression were significantly reduced in tissues from FD patients compared with controls. MC degranulation and tryptase decreased the TEER and reduced the expression of TJ proteins in Caco-2 cell monolayers. A PAR-2 antagonist and an ERK1/2 signaling pathway inhibitor significantly reduced the effect of MC degranulation on the TEER and TJ protein expression in Caco-2 cell monolayers. Conclusions MCs disrupt duodenal barrier function by modulating the levels of TJ proteins, and the PAR-2 and ERK1/2 signaling pathways may mediate the pathogenesis of FD.
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