Bioinformatic analysis by ANDSystem revealed members of IL-6 signaling pathway initiated by glucose variability and involved in diabetic retinopathy

Background and Aim: There is now growing evidence that complications of diabetes, including diabetic retinopathy (DR), are closely related to glucose variability (GV). Analysis of gene networks revealed that interleukin-6 (IL-6) is an important player connecting GV and DR. The precise molecular mechanisms connecting DR with GV still have to be clarified. The aim of this work was to find the members of human IL-6 signal transduction pathway initiated by GV and involved in DR. Materials and Methods: Reconstruction and analysis of signal pathways and gene networks were performed using the ANDSystem. Gene Ontology enrichment analysis was done by DAVID service. Results: Using bioinformatics analysis by ANDSystem, a link between GV and DR was found and 73 key genes that are involved in IL-6 signaling pathway were defined. Among them, we identified genes of cytokines, chemokines, growth factors, hormones, enzymes, receptors, binding proteins and microRNA. These genes are involved in inflammation, cell-cell signaling, angiogenesis, response to hypoxia, and aging. Genes FAAH, LIPG, AQP4, and NOX1 were found to be the most specifically related to IL-6 signaling pathway in DR according to CTS specificity coefficient calculated by ANDSystem. Conclusion: It was shown that IL-6 signaling plays an important role in the DR development during excessive GV. This raises the understanding of the molecular mechanisms of DR pathogenesis under condition of high GV.