Ceria Nanoparticles Ameliorate Renal Fibrosis by Modulating the Balance Between Oxidative Phosphorylation and Aerobic Glycolysis

Abstract Background and aims: Renal fibrosis is the common outcome in all progressive forms of chronic kidney disease. Unfortunately, the pathogenesis of the renal fibrosis remains largely unexplored, among which metabolic reprogramming plays an extremely crucial role in the evolution of renal fibrosis. Ceria nanoparticles have strong ROS scavenging and anti-inflammatory activity. The present study aims to determine whether CeNPPEG has therapeutic value for renal fibrosis.Methods: Ceria nanoparticles and Ceria nanoparticles-PEG were synthesized according to previously reported procedures with slight modifications. For the in vivo studies, unilateral ureteral obstructive -induced kidney fibrosis was chosen. Through cellular studies, TGF-β1-induced epithelial-to-mesenchymal transition in HK-2 cells of enhanced glycolysis was initially utilized to report the associations among Ceria nanoparticles-PEG, oxidative phosphorylation, glycolysis and renal fibrosis.Results: In this study, Ceria nanoparticles were developed and the Ceria nanoparticles-PEG treatment significantly ameliorated renal fibrosis in unilateral ureteral obstructive mice as well as protected HK-2 cells from transforming growth factor beta1 -induced epithelial-to-mesenchymal transition process. Furthermore, we found that Ceria nanoparticles-PEG suppressed hexokinase 1and hexokinase 2 to block the dysregulated metabolic status, in which damaged epithelial cells take glycolytic metabolism as priority to oxidative phosphorylation, exerting the protective function in the progress of renal fibrosis.Conclusions: The application of Ceria nanoparticles-PEG in this study is attempted to provide another therapeutic option on renal fibrosis.