Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis

Journal of Nanobiotechnology

Feng Zeng¹  Dongliang Zhang²  Xiaolin Sun²  Hong Xin²  Ping Hu²  Yinhang Wang²  Fengling Ning²  Shilin Zhou²  Xuemei Zhang²  Jiaqi He²  Mengling Wang²  Xudong Xu²  Cong Li²  Svetlana Reilly³  Cong Wang⁴  Jisheng Xiao⁵ 

[1] Artemisinin Research Center, Institute of Science and Technology, The First Clinical Medical School, Lingnan Medical Research Center, The First Affiliated Hospital, Guangzhou University of Chinese Medicine;Department of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan University;Division of Cardiovascular Medicine, Department of Medicine, University of Oxford, John Radcliffe Hospital;Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China, Academy for Engineering and Technology, Fudan University;Science and Technology Innovation Center, Guangzhou University of Chinese Medicine;

关键词: Ceria nanoparticles;    Metabolic reprogramming;    Oxidative phosphorylation;    Aerobic glycolysis;    Renal fibrosis;   

DOI  :  10.1186/s12951-021-01122-w

来源: DOAJ

【 摘 要 】

Abstract Background and aims Renal fibrosis is the common outcome in all progressive forms of chronic kidney disease. Unfortunately, the pathogenesis of renal fibrosis remains largely unexplored, among which metabolic reprogramming plays an extremely crucial role in the evolution of renal fibrosis. Ceria nanoparticles (CeNP-PEG) with strong ROS scavenging and anti-inflammatory activities have been applied for mitochondrial oxidative stress and inflammatory diseases. The present study aims to determine whether CeNP-PEG has therapeutic value for renal fibrosis. Methods The unilateral ureteral obstructive fibrosis model was used to assess the therapeutic effects in vivo. Transforming growth factor beta1-induced epithelial-to-mesenchymal transition in HK-2 cells was used as the in vitro cell model. The seahorse bioscience X96 extracellular flux analyzer was used to measure the oxygen consumption rate and extracellular acidification rate. Results In the present study, CeNP-PEG treatment significantly ameliorated renal fibrosis by increased E-cadherin protein expression, and decreased α-SMA, Vimentin and Fibronectin expression both in vitro and in vivo. Additionally, CeNP-PEG significantly reduced the ROS formation and improved the levels of mitochondrial ATP. The seahorse analyzer assay demonstrated that the extracellular acidification rate markedly decreased, whereas the oxygen consumption rate markedly increased, in the presence of CeNP-PEG. Furthermore, the mitochondrial membrane potential markedly enhanced, hexokinase 1 and hexokinase 2 expression significantly decreased after treatment with CeNP-PEG. Conclusions CeNP-PEG can block the dysregulated metabolic status and exert protective function on renal fibrosis. This may provide another therapeutic option for renal fibrosis. Graphical Abstract

【 授权许可】

Unknown