Angiotensin II–Induced Ferroptosis in Epithelial Cells Contributes to Kidney Injury via SP1-DPEP1–Mediated SLC3A2 Degradation
This study investigated the role of ferroptosis in angiotensin II (AngII)-induced kidney injury, addressing a critical gap in understanding AngII-mediated nephropathy mechanisms. We asked whether dipeptidase 1 (DPEP1)-mediated SLC3A2 degradation drives ferroptosis and renal damage under AngII activation. AngII upregulates DPEP1 via SP1, promoting SLC3A2 ubiquitination and glutathione depletion, ultimately triggering tubular ferroptosis. DPEP1 inhibition rescues renal function. Targeting the SP1-DPEP1-SLC3A2 axis offers a novel therapeutic strategy against ferroptosis-dependent kidney injury in hypertension and metabolic disorders.
Authors
- Qihe Zhang
- Yanru Li (ORCID: https://orcid.org/0000-0003-2922-3841)
- Ying Xin (ORCID: https://orcid.org/0000-0002-9008-6105)
- Shaohua Li (ORCID: https://orcid.org/0000-0001-7399-821X)
- Haiying Zhang (ORCID: https://orcid.org/0000-0002-7158-2373)
- Chao Dong (ORCID: https://orcid.org/0000-0003-4612-5127)
- Shuang Lv
- Yuan Tian
- Xin Jiang
- Ge Yang
Institutions
- Jilin University (CN)
- First Hospital of Jilin University (CN)
- Second Affiliated Hospital of Jilin University (CN)
- Ministry of Education (KN)
Publication Details
- Journal
- Diabetes
- Published
- 2026-01-05
- DOI
- https://doi.org/10.2337/db25-0619
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Jilin University