Bioinformatics Analysis Of The Molecular Mechanism Involved In The Inflammatory Cytokine-induced Pancreatic ?-cells Dysfunction And Apoptosis

Type 1 diabetes mellitus is an autoimmune disease mediated by T cell,characterized by specific injury of islet beta cells.A large number of inflammatory cytokines are involved in type 1 diabetes mellitus.Immune cells which infiltrate pancreatic islet such as macrophages,lymphocytes,producing large amounts of inflammatory cytokines.These inflammatory cytokines can induce islet beta cells apoptosis and insulin secretion defect and then play an important role in the occurrence and development of type 1 diabetes mellitus.The development process of type 1 diabetes mellitus involves a variety of molecule functions and biological processes related with gene expression patterns and their interaction relationships.Studying on these molecule functions and biological processes has an important significance for revealing the pathogenesis mechanism of type 1 diabetes mellitus and for research and development in the medicines of Type 1 diabetes mellitus.Traditional biology experimental methods are possible to detect the expression and distribution of protein effectively,but the efficiency of the experiments are not high,generally focus on the mechanism of a single molecule,unable to recognize the mechanisms of drug molecules from the system level.Using gene microarray can simultaneously detect genome-wide gene expression.Through gene microarray data analysis,hundreds to thousands of differentially expressed genes related to the pathways can be selected.Using systems biology approaches to research the pathogenesis of type 1 diabetes mellitus can deduce the pathways and biological functions affected by inflammation cytokines through the difference between gene expression and regulation of normal islet cells and inflammatory cytokines treated islet cells,then elaborate the damage and apoptosis mechanism of islet beta cell induced by inflammatory cytokines and thus fill up the deficiency of traditional experimental methods.With the development of omics experiments technology and the reduction of experimental costs,systems biology approach has became the main method of the research in pathogenesis and new drugs of type1 diabetes mellitus.In precent paper,through bioinformatics analysis of the gene microarray data of islet beta cells treated with the inflammatory cytokines IL-1? combined with IFN-?and normal pancreatic islet beta cells,differentially expressed genes at a series of time points were selected.The further pathway enrichment analysis of the differentially expressed genes indicated that inflammatory cytokines IL-1? and IFN-? induce islet beta cell apoptosis and insulin secretion functional defect mainly through cell cycle arrest,DNA damage and i NOS-NO pathways.Moreover it was found that a new transcriptional regulation factor miR-21 was significantly suppressed by the analysis of the upstream regulation ofdifferentially expressed genes.As miR-21 has an inhibiting role in islet beta cells apoptosis induced by IFN-?,therefore it was conjectured that miR-21 may play an important role in the process of islet beta cells apoptosis induced by inflammatory cytokines.Finally,through GO function clustering and IPA pathway analysis of the differentially expressed genes,a mechanism model of islet beta cells apoptosis induced by inflammatory cytokines is build and further analysis and demonstration about the correctness of the model were made by literature search and evaluation.