PUBLICATION
Cobaltosic oxide-polyethylene glycol-triphenylphosphine nanoparticles ameliorate the acute-to-chronic kidney disease transition by inducing BNIP3-mediated mitophagy
- Authors
- Qin, S., Liu, C., Chen, Y., Yao, M., Liao, S., Xin, W., Gong, S., Guan, X., Li, Y., Xiong, J., Chen, J., Shen, Y., Liu, Y., Zhao, J., Huang, Y.
- ID
- ZDB-PUB-230223-53
- Date
- 2023
- Source
- Kidney International 103(5): 903-916 (Journal)
- Registered Authors
- Liu, Chi
- Keywords
- BNIP3, COPT, acute kidney injury, chronic kidney disease, mitophagy
- MeSH Terms
-
- Acute Kidney Injury*/pathology
- Animals
- Membrane Proteins/metabolism
- Mice
- Mitochondrial Proteins/metabolism
- Mitophagy
- Renal Insufficiency, Chronic*/drug therapy
- Zebrafish/metabolism
- PubMed
- 36805450 Full text @ Kidney Int.
Citation
Qin, S., Liu, C., Chen, Y., Yao, M., Liao, S., Xin, W., Gong, S., Guan, X., Li, Y., Xiong, J., Chen, J., Shen, Y., Liu, Y., Zhao, J., Huang, Y. (2023) Cobaltosic oxide-polyethylene glycol-triphenylphosphine nanoparticles ameliorate the acute-to-chronic kidney disease transition by inducing BNIP3-mediated mitophagy. Kidney International. 103(5):903-916.
Abstract
Accumulating evidence highlights mitochondrial dysfunction as a crucial factor in the pathogenesis of acute kidney injury (AKI), thus novel therapeutic strategies maintaining mitochondrial homeostasis are highly anticipated. Recent studies have shown that cobaltosic oxide has peroxidase-like catalytic activities, although its role and mechanism remain elusive in AKI. In the present study, we synthesized and identified cobaltosic oxide-polyethylene glycol-triphenylphosphine (COPT) nanoparticles by conjugating cobaltosic oxide with polyethylene glycol and triphenylphosphine, to improve its biocompatibility and mitochondria-targeting property. We found that COPT preferentially accumulated in the kidney proximal tubule cells, and significantly alleviated ischemic AKI in mouse models and gentamicin induced-AKI in zebrafish model. COPT also inhibited the transition from AKI to chronic kidney disease (CKD), with few side effects. Further studies demonstrated that COPT localized in the mitochondria, and ameliorated hypoxia-reoxygenation-mediated mitochondrial damage through enhancing mitophagy in vitro and in vivo. Mechanistically, COPT dose-dependently induced the expression of Bcl-2/adenovirus E1B 19-kDa interacting protein (BNIP3), while knockdown of BNIP3 attenuated COPT-induced mitophagic flux and mitochondrial protection. Thus, our findings suggest that COPT nanoparticles ameliorate AKI and its progression to CKD through inducing BNIP3-mediated mitophagy, indicating that COPT may serve as a promising mitochondria-targeting therapeutic agent against AKI.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping