RNAs sequencing of human kidney reveals CXCL10 deficiency in patients with non-proteinuric diabetic nephropathy

The non-typical phenotype of non-proteinuric diabetic nephropathy (NP-DN), as a specific phenotype of DN, has been increasingly recognized. However, the mechanism of these patients remains unclear. In this study, we will identify important disease-related genes in NP-DN patients by transcriptomics at the level of renal histology. Paraffin-embedded kidney tissues, including kidney biopsy tissues from DN patients with albuminuria > 3.5 g/d (DN groups, n = 6), NP-DN patients with albuminuria < 0.2 g/d (NP-DN groups, n = 6), and normal kidney tissues from non-diabetic renal cancer patients undergoing surgical resection (control groups, n = 6), were used for RNA sequencing. Differentially expressed genes (DEGs) up-regulated and down-regulated significantly only in the NP-DN group were selected for further analysis. A protein–protein interaction (PPI) network was established to identify key DEGs. Immunohistochemistry (IHC) staining of renal tissues was performed to validate the accuracy of the bioinformatic results. Furthermore, these key DEGs were confirmed by ELISA in plasma. A total of 1791 DEGs up-regulated and down-regulated significantly only in the NP-DN group were selected for bioinformatic analysis. Three significantly down-regulated genes, CXCL9, CXCL10, and CXCL11, were identified in NP-DN patients by PPI network. The results of ELISA showed that the level of CXCL10 in the NP-DN group was significantly lower than that in the control group and the DN group (P < 0.001), which was consistent with the expression tendency of bioinformatic results. However, there were no significant differences in CXCL9 and CXCL11 among the three groups (P = 0.063 and P = 0.351). IHC staining was in line with the expression tendency of ELISA results. Our findings suggest that the CXCL10 signaling pathway may play a unique role in the development of NP-DN. However, its specific functions require clarification through future functional studies.