2. Academic Validation
  3. Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model

Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model

  • Cell Death Discov. 2022 Mar 22;8(1):127. doi: 10.1038/s41420-022-00931-8.
Jingyu Wang 1,  Yaqing Wang 1,  Yi Liu 2,  Xintian Cai 3,  Xin Huang 1,  Wenjing Fu 1,  Lei Wang 1 4,  Lihua Qiu 5,  Junying Li 5,  Li Sun 6
Affiliations

Affiliations

  • 1 Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, 110000, Liaoning Province, People's Republic of China.
  • 2 Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan Province, People's Republic of China.
  • 3 Department of Graduate School, Xinjiang Medical University, Urumqi, 830054, Xinjiang Province, People's Republic of China.
  • 4 Department of Nephrology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110000, Liaoning Province, People's Republic of China.
  • 5 Department of epigenetics, China Medical University, Shenyang, 110000, Liaoning Province, People's Republic of China.
  • 6 Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, 110000, Liaoning Province, People's Republic of China. [email protected].
PMID: 35318301 DOI: 10.1038/s41420-022-00931-8
Abstract

Ferroptosis is a non-traditional form of regulated cell death, characterized by iron overload and lipid peroxidation. Exploration of Ferroptosis in chronic kidney disease (CKD) has been extremely limited to date. In this study, we established a rat model of CKD by 5/6 nephrectomy, treated CKD rats with the Ferroptosis inducer, cisplatin (CDDP), and the Ferroptosis inhibitor, deferoxamine mesylate (DFO), and observed the resulting pathologic changes (injury markers and fibrosis) and ferroptotic biochemical indices. Kidney iron deposition, lipid peroxidation, mitochondrial defects, Ferroptosis marker induction, and TUNEL staining positivity were detected in CKD group rats. Further, treatment with CDDP or DFO influenced renal injury and fibrosis by affecting Ferroptosis, rather than Apoptosis, and Ferroptosis occurs in the remnant kidney due to disordered iron metabolism. In conclusion, our study shows for the first time that 5/6 nephrectomy induces Ferroptosis in the remnant kidney and clarifies the underlying pathogenesis. Moreover, we demonstrate that Ferroptosis is involved in CKD progression and represents a therapeutic target in chronic kidney injury and renal fibrosis.

Figures
Products