Mechanism of ferroptosis in hypertensive nephropathy

Yongzhi Chen; Kun Wang; Jie Yang; Aixia Zhang; Xiayun Dong; Zhaocheng Zhou; Tianshu Li; Ruixia Fan

doi:10.21037/tau-22-276

Mechanism of ferroptosis in hypertensive nephropathy

Transl Androl Urol. 2022 May;11(5):617-626. doi: 10.21037/tau-22-276.

Authors

Yongzhi Chen^#¹, Kun Wang^#², Jie Yang¹, Aixia Zhang², Xiayun Dong², Zhaocheng Zhou², Tianshu Li², Ruixia Fan²

Affiliations

¹ Department of Cardiology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
² School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

^# Contributed equally.

Abstract

Background: In recent years, it has been demonstrated that ferroptosis can be involved in a variety of kidney injury processes, but the role played by ferroptosis in hypertensive kidney injury is still unclear. The aim was to explore the mechanism of ferroptosis playing a role in hypertensive kidney disease and related signalling pathways.

Methods: GSE37455 microarray data was downloaded from the Gene Expression Omnibus (GEO) database and preprocessed. Batch correction and differential analysis were performed on the normal population and the hypertensive nephropathy samples using the "sva" and "limma" packages in R software. Ferroptosis-related genes were obtained from the FerrDb database and normalized and processed using UniProt. Ferroptosis-related differentially expressed genes were obtained using Venny 2.1. and imported into the Search Tool for the Retrieval of Interacting Genes (STRING) to obtain protein-protein interactions (PPIs). The data were imported into Cytoscape 3.7.2 for processing to identify the core differential genes of ferroptosis based on nodes. Gene set enrichment analysis (GSEA) was performed on the core differential genes of ferroptosis to infer the pathway of ferroptosis action in hypertensive nephropathy.

Results: The R software processing yielded 37 differential genes, including 13 upregulated genes and 24 downregulated genes. 202 ferroptosis-related genes were obtained by screening, and 3 ferroptosis-related differentially expressed genes were obtained after taking the intersection. The ferroptosis-related core differentially expressed gene albumin (ALB) was obtained by PPI network analysis and Cytoscape processing. GSEA analysis revealed that ferroptosis may act in hypertensive nephropathy through pathways such as drug metabolism-cytochrome P450, branched-chain amino acid (BCAA) metabolism, retinol metabolism, and biological processes (BPs) such as organic and amino acid metabolism and humoral immunity.

Conclusions: Ferroptosis may act in the development of hypertensive nephropathy through pathways such as BCAA metabolism and retinol metabolism and BPs such as organic and amino acid metabolism and humoral immunity.

Keywords: Bioinformatics; ferroptosis; hypertensive nephropathy; mechanism of action.