Bioinformatics analysis of genes related to iron death in diabetic nephropathy through network and pathway levels based approaches

Abstract

Diabetic nephropathy is one of the common microvascular complications of diabetes. Iron death is a recently reported way of cell death. To explore the effects of iron death on diabetic nephropathy, iron death score of diabetic nephropathy was analyzed based on the network and pathway levels. Furthermore, markers related to iron death were screened. Using RNA-seq data of diabetic nephropathy, samples were clustered uniformly and the disease was classified. Differentially expressed gene analysis was conducted on the typed disease samples, and the WGCNA algorithm was used to obtain key modules. String database was used to perform protein interaction analysis on key module genes for the selection of Hub genes. Moreover, principal component analysis method was applied to get transcription factors and non-coding genes, which interact with the Hub gene. All samples can be divided into two categories and principal component analysis shows that the two categories are significantly different. Hub genes (FPR3, C3AR1, CD14, ITGB2, RAC2 and ITGAM) related to iron death in diabetic nephropathy were obtained through gene expression differential analysis between different subtypes. Non-coding genes that interact with Hub genes, including hsa-miR-572, hsa-miR-29a-3p, hsa-miR-29b-3p, hsa-miR-208a-3p, hsa-miR-153-3p and hsa-miR-29c-3p, may be related to diabetic nephropathy. Transcription factors HIF1α, KLF4, KLF5, RUNX1, SP1, VDR and WT1 may be related to diabetic nephropathy. The above factors and Hub genes are collectively involved in the occurrence and development of diabetic nephropathy, which can be further studied in the future. Moreover, these factors and genes may be potential target for therapeutic drugs.

Integrative analyses of biomarkers and pathways for diabetic nephropathy

“…In our study, Transcription factors HIF1A, KLF5, RUNX1, SP1, SPI1, STAT1, MBD1 and WT1 may be related to diabetic nephropathy. The results were similar to previous studies ( Hu et al, 2021 ). Chronic hyperglycemia can lead to microcirculatory disorders presenting with renal ischemia and hypoxia, and hypoxia can lead to inhibition of HIF-1α stability and function and decreased renal hypoxia tolerance.…”

Identification of Genes Reveals the Mechanism of Cell Ferroptosis in Diabetic Nephropathy

“…Meanwhile, this study used TRRUST V2 (www. grnpedia.org/) database to predict transcription factor (TF)-Gene (protein) interaction (Hu et al, 2021). Additionally, ubibrowser 2.0 (http://ubibrowser.ncpsb.org.cn/) was used to observe proteins involved in the ubiquitination process of target proteins.…”

VDR Activation Attenuates Renal Tubular Epithelial Cell Ferroptosis by Regulating Nrf2/HO‐1 Signaling Pathway in Diabetic Nephropathy

“…Recently, Hu et al reported that the vitamin D receptor (VDR) might be a transcription factor related to ferroptosis in DN. [14] Accumulating evidence has revealed the nephroprotective effect of VDR activation, including immune regulation, inflammatory inhibition and fibrosis alleviation. [15][16][17] Paricalcitol (PAR) is an active form of VD for the treatment of kidney diseases.…”