The Effect And Mechanism Exploration Of BAHD1in Ulcerative Colitis

Background&Aims:Ulcerative colitis (UC) is a common inflammatory bowel disease (IBD) producing intestinal inflammation and tissue damage. The precise etiology of UC remains unknown. In this study, we applied a computational approach to discover novel genes associated with UC, based on publicly available data, aiming to validate the underlying mechanism novel gene in UC.Methods:In this study, we applied a rank-based expression profile comparative algorithm, gene set enrichment analysis (GSEA), to evaluate expression profiles of UC patients and small interfering RNAs (siRNAs) perturbed cells to predict proteins that might be essential in UC, from publicly available expression profiles. We used quantitative PCR (qPCR) to characterize the expression levels of those predicted to be the most potential genes for UC in dextran sodium sulfate (DSS)-induced colitis in mice. The most probable potential colitis-related siRNA, bromo adjacent homology domain (BAHD1), and its molecular mechanism were investigated by western blotting in a cell model of gut inflammation.Results:Based on GSEA, five genes whose single siRNA perturbation had smallest distances to UC were EZH2, UPF1, FOXM1, NUDT6, BAHD1.(1) Establishment of DSS-induced colitis in mice.(2) Establishment of a cell model to simulate inflammatory environment for IECs.(3) BAHD1decreased in vivo and in vitro models and UC patients.(4) Associated inflammatory mediators were enhanced in BAHD1-deficient Caco-2cell model.(5) Activation of Ikappa B(IκB) Kinase(IKK)/NF-κB and JNK/AP-1pathways and Caspase-8in siBAHDl-treated Caco-2Cell model.(6) BAHD1differentially modulated the TNF signaling pathway by altering TNFR1expression.Conclusion:Our findings indicate that the computational approaches leveraging public gene expression data can be used to infer potential genes or proteins for diseases and BAHD1might act as an indispensable factor in regulating cellular inflammatory response in UC:(1) BAHD1decreased in vivo and in vitro models and UC patients;(2) BAHD1repression resulted in continuous excessive immune response in IECs.(3) BAHD1might modulate TNFR1expression to keep homeostasis in gut.