Based on the latest statistics in the year 2017, a total of 451 million people have diabetes, and it is expected that by 2045, this figure will reach 693 million . Diabetic nephropathy is one of the most serious microvascular complications. DN has become the main cause of the end-stage renal disease (ESRD) in many countries. The current treatment is not managed to cure DN and prevent the progression to ESRD. In recent years, bioinformatics data have been widely used to study the mechanism of disease and to predict the possible therapeutic targets. In this study, bioinformatics was used to analyze the gene expression between patients with diabetic nephropathy and normal subjects. Through screening of core genes and gene annotation, the up-regulated differentially expressed genes were significantly enriched in immune inflammatory-related signaling pathways. Thus, this implicated that the function of differentially expressed genes is closely related to the signal pathway of immune inflammation. This attributed that the pathological mechanism of diabetic nephropathy is mainly caused by inflammatory stimulation leading to cell damage. The risk factors for the release of renal cells can trigger the remodeling process by stimulating the renal cells and activating the immune cells of the congenital and adaptive system.
In this study, GO and KEGG were used to annotate the core genes. Consistent finding was found in which the core genes were mainly related to the immune-inflammatory signaling pathway. This had further suggested that the immune system involving in the inflammatory mediating process reaction is the key factor in the pathogenesis of diabetic nephropathy. The key genes concerning DN were CXCL-8, MMP-9, IL-1B, IL-6, and ATF3.
CXCL8 (IL-8) is a cytokine derived from a variety of cells and has a variety of biological functions. It can induce leukocyte chemotaxis and activation, lysosomal release activation and chemotaxis. High glucose can stimulate the production of CXCL8 and excrete into the urine, which is significantly correlated with the level of HbA1c, but not with the stage of disease or pathological damage. Based on the finding, we may stipulate that CXCL8 will be increased in the early stage of diabetic nephropathy to evaluate the degree of renal damage in patients with type 2 diabetic nephropathy[5–6].
MMP-9, the ninth member of the MMP family, may play an important role in leukocyte migration and local proteolysis of the extracellular matrix. Many studies have shown that MMP-9 is an important inflammatory marker involved in the pathophysiological process of DN. Studies have shown that MMP9 can delay glomerulosclerosis and interstitial fibrosis by increasing ECM degradation, thereby slowing down the progression of DN .
IL-1B is one of the three cytokines produced by interleukin-1, which is involved in a variety of inflammatory processes. It is related to IgA nephropathy, diabetic nephropathy and other kidney diseases. Studies have shown that the relationship between IL-1B and DN can be explained by the biological characteristics of IL-1. IL-1 is an important proinflammatory cytokine and is increased in diabetic nephropathy. Monika Buraczynska suggested that in diabetic nephropathy patients and mouse models, the activation of IL-1 involved in the regulation of cytokine production and the activation of extracellular matrix may play an important role in the progression of renal failure in diabetic patients .
IL-6 is a cytokine with multiple functions, which plays an important role in inflammation and immune response. Senthilkumar et al. found that IL-6 levels in diabetic nephropathy patients were significantly higher .
ATF3 is a stress-induced transcription factor, which is transiently expressed after stimulation. Studies have shown that in diabetic nephropathy, the expression of AFT3 is significantly increased .