Ferroptosis in renal fibrosis: a mini-review

Abstract

Ferroptosis is a novel form of programmed cell death that is iron-dependent and distinct from autophagy, apoptosis, and necroptosis. It is primarily characterised by a decrease in glutathione peroxidase 4 (GPX4) activity, or by the accumulation of lipid peroxidation and reactive oxygen species (ROS). Renal fibrosis is a common pathological change in the progression of various primary and secondary renal diseases to end-stage renal disease and poses a serious threat to human health with high morbidity and mortality. Multiple pathways contribute to the development of renal fibrosis, with ferroptosis playing a crucial role in renal fibrosis pathogenesis due to its involvement in the production of ROS. Ferroptosis is related to several signalling pathways, including System Xc-/GPX4, abnormal iron metabolism and lipid peroxidation. A number of studies have indicated that ferroptosis is closely involved in the process of renal fibrosis caused by various kidney diseases such as glomerulonephritis, renal ischaemia-reperfusion injury, diabetic nephropathy and renal calculus. Identifying the underlying molecular mechanisms that determine cell death would open up new insights to address a therapeutic strategy to renal fibrosis. The review aimed to browse and summarise the known mechanisms of ferroptosis that may be associated with biological reactions of renal fibrosis.

Keywords:

• Renal fibrosis
• ferroptosis
• iron metabolism
• regulated cell death
• kidney diseases

Acknowledgments

The figures in this review were created with Adobe Illustrator 2022.

Author’s contributions

Si-Qi Yang: Wrote the manuscript. Xi Zhao and Jing Zhang: Collect and organise literature, proofread the manuscript. Yu-Han Wang and Dong-Ying Liao: Provide new ideas and opinions for revising the manuscript and participate in collecting and organising literature. Yao-Guang Wang: Fully responsible for the study designing, research fields, drafting, and finalising the paper.

Disclosure statement

All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (grant numbers 81603544, 81573888), National Famous Traditional Chinese Medicine Expert Inheritance Studio (grant numbers 978022) and Inheritance and development of traditional Chinese medicine: Famous Traditional Chinese Medicine Expert Inheritance Studio of Tianjin (grant numbers 883022).