Mechanisms Of Endoplasmic Reticulum Stress Regulating NADPH Oxidase Expression In Crohn's Disease

Objective: The purpose of this study was to explore the role and possible mechanism of ERS in regulating NADPH oxidase expression in Crohn's disease,and to provide new therapeutic basis and ideas for the treatment and prevention of related diseases and their complications.Methods: 10 surgical specimens of CD patients were selected as experimental group,and 10 surgical specimens of adjacent intestinal mucosa of colon cancer patients were selected as control group.Masson staining was used to observe the pathological changes of intestinal tissue and the degree of fibrosis.Then the expression of GRP78 protein and P47 PHOX protein in intestinal specimens was detected by immunohistochemistry.In CD group,the correlation between the degree of Masson fibrosis and the expression of GRP78 protein and P47 PHOX protein was analyzed.The expression of GRP78 and P47 PHOX in intestinal epithelial cells stimulated by Tm was detected by Western blot,and whether different concentrations of 4PBA could inhibit the expression of GRP78 and P47 PHOX.Finally,the expression of P47 PHOX protein was detected by inhibiting IRE1 alpha-XBP1 S,IRE1 alpha-TRAF2-JNK and PERK-eIF2 alpha in different ERS pathways.Results: 1.The degree of intestinal fibrosis in CD patients was higher than that in control group by Masson staining.2.Compared with normal intestinal mucosa adjacent to colon cancer,the expression of GRP78 and P47 PHOX in Crohn's disease intestinal mucosa was significantly increased in immunohistochemical tests.3.In Crohn's disease group,there was a strong positive correlation between the degree of Masson fibrosis and the expression of GRP78 and P47 PHOX proteins.4.In vitro,ERS induced Tm,and the expression of GRP78 protein and P47 PHOX protein increased,while 4PBA could inhibit.5.Inhibiting IRE1?-TRAF2-JNK,PERK-eIF2? pathway could down-regulate P47 PHOX protein,while inhibiting IRE1 ?-XBP1 S could up-regulate the expression of P47 PHOX protein.CONCLUSION: 1.The expression of GRP78 and P47 PHOX in CD is significantly increased,and is positively correlated with the degree of fibrosis,s?ggesting that ERS may participate in the pathogenesis of CD by up-regulating OS.2.ERS may induce OS positively thro?gh IRE1 alpha-TRAF2-JNK and PERK-eIF2 alpha pathways,while IRE1 alpha-XBP1 S pathway plays a negative regulatory role.