The Role Of DJ-1 In The Pathogenesis Of Ulcerative Colitis

Background:Ulcerative colitis(UC)is a chronic non-specific inflammatory disease.In recent years,the incidence of Chinese population has increased significantly.However,the etiology and pathogenesis of UC are still unclear.This study aimed to explore the role of DJI in the development of UC and whether DJ1 can be regulated by P53 through relevant experimental methods.Methods:UC in vitro(inflammation model,apoptosis model and co-culture barrier model)and in vivo models(DSS models)were established,and RNA interference and recombinant adenovirus technology were used to inhibit or enhance the expression of DJI in in vitro models.The DJ1-/-mouse model was also used.The mRNA,protein and activity of DJI were detected by real-time PCR(qRT-PCR)and WB.The expression of DJI and inflammatory cells in intestinal mucosal epithelial cells were detected by immunohistochemistry.The cell loss,apoptosis and intestinal barrier function were detected.Our goal is to observe the effects of DJI on the colonic inflammation,apoptosis,cell damage and intestinal mucosal barrier function by these molecular biology methods.The effects of DJ1 and P53 on colonic epithelial cell inflammation and apoptosis were ulteriorly analyzed.Results:First,the expression of DJ1 was significantly decreased in UC cell model and DSS animal model(mRNA1.015 VS 0.840,p<0.05;mRNA NC=1.062 VS 3.5%DSS=0.540 VS 4%DSS=0.303,P<0.05).Subsequently,the expression of DJI was downregulated in the colon mucosa of human UC by immunohistochemical method(IOD NC 0.317±0.023 VS CD 0.234±0.007 VS UC 0.211±0.004,P<0.05).The expression of TNF-a,iNOS and IL-6 were significantly increased under low expression DJI induced cell model(3.549± 0.333 VS 7.376±0.425 P<0.05;7.877±0.366 VS 11.300±0.565,P<0.001;1.596±0.371 VS 2.807±0.215,P<0.05),and the degree of cell damage and apoptosis were significantly worse than before(LDH 0.752±0.003 VS 0.974 ± 0.022 P<0.001;caspase3/7 activity 1.784±0.082 VS3.918 ± 0.046,P<0.001).Otherwise,under overexpressing DJI induced cell model,the expression of TNF-a,iNOS,IL-6 was decreased(20.840±0.055 VS 11.280±0.969,P<0.001;29.780±1.571 VS 19.250±1.548,P<0.01;8.116 ± 0.471 VS 5.489±0.323,P<0.01).Under DJ1-/-mouse UC model,the higher expression of TNF-a(4.490±0.892 VS 25.070±9.140,P<0.001)in serum,the shorter length of the colon(6.200±0.260 VS 5.100±0.055,P<0.05),the severer intestinal inflammation(IL-6:2.281±0.421 VS 23.400±5.744,P<0.001;IL-1?:4.232±1.083 VS 12.660±1.545 P<0.0001;MCP-1:2.261±0.3462 VS 14.900±3.673,P<0.001)were detected than before.In addition,the expression of colonic epithelial neutrophils and macrophages was significantly increased.Moreover,intestinal tight junction damage was more serious and tight junction protein claudin expression was significantly reduced.Finally,based on the low expression of DJ1,further inhibiting the expression of P53 to construct a UC cell model,we found that the cell damage was relieved(LDH:0.814±0.005 VS 0.626±0.003,P<0.001).Conclusion:DJ1 decreased in vivo and in vitro models and LJC patients;DJ1 repression aggravate colonic cell inflammation,apoptosis,cell damage and intestinal mucosal barrier function,suggesting that DJI may play a protective role in the development of UC,and its role may be achieved by regulating downstream P53.DJ1 may become a potential molecular therapeutic target for UC.