Identification of ferroptosis‑associated genes in chronic kidney disease.

Abstract

Ferroptosis serves a pivotal role in developing chronic kidney disease (CKD). The present study aimed to detect and confirm the relevance of potential ferroptosis-related genes in CKD using bioinformatics and experimentation strategies. The original GSE15072 mRNA expression dataset was retrieved from the Gene Expression Omnibus database. Subsequently, the potential differentially expressed genes associated with ferroptosis of CKD were screened using R software. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses, correlation analysis and protein-protein interactions (PPI) were performed for differentially expressed ferroptosis-associated genes (DFGs). Lastly, the expression levels of the top nine DFGs were measured in the kidney tissue of Adriamycin-induced CKD rats and healthy controls via reverse transcription-quantitative (RT-q)PCR analysis. Overall, 49 DFGs among 21 patients with CKD and nine healthy controls were identified. GO and KEGG enrichment analyses demonstrated that these DFGs were primarily involved in 'ferroptosis' and 'mitophagy'. PPI findings indicated that these ferroptosis-associated genes interacted with one another. RT-qPCR of CKD tissue from the rat model revealed that STAT3, MAPK14, heat shock protein (HSP)A5, MTOR and solute carrier family 2 member 1 (SLC2A1) mRNA levels in CKD were upregulated. Overall, 49 potential ferroptosis-associated genes of CKD were identified via bioinformatics analyses. STAT3, MAPK14, HSPA5, MTOR and SLC2A1 may influence CKD onset by regulating ferroptosis. The present results add to the existing body of knowledge about CKD and may be useful in the treatment of CKD.