Identification of Fibrotic Biomarkers Associated with Macrophages in Diabetic Nephropathy.

Abstract

BACKGROUND Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Renal fibrosis is an important pathological feature of kidney injury, and the therapeutic means are very limited. The functions of macrophages play important roles in renal fibrosis. There is a complicated link between altered immune metabolism and oxidative stress. Hence, we designed this study to identify the oxidative stress- and macrophage-relevant biomarkers reflecting fibrosis in DN. MATERIAL AND METHODS Differential expression analysis was performed based on the GSE96804 dataset. xCell and weighted gene co-expression network analysis were used to determine the distinctions in infiltrating immune cells between DN and control specimens. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted. A protein-protein interaction network was constructed to identify the hub genes. Hub genes were validated in an external dataset, GSE30528, and cell models. RESULTS MMP2, CASP3, and HIF-1alpha were identified as biomarkers, which were upregulated in the DN group and positively correlated with the infiltration of macrophages and M1 macrophages. In vitro, the 3 genes were highly expressed in murine MPC5 cells treated with high glucose and human THP-1 macrophages treated with advanced glycation end products. CONCLUSIONS Our results provided biomarkers for predicting the fibrotic progression of DN and confirmed that MMP2, CAPS3, and HIF-1alpha have good diagnostic value. They might be involved in the progression of DN fibrosis by regulating oxidative stress and macrophage recruitment or polarization.