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 renal fibrosis remains largely unexplored, among which metabolic reprogramming plays an extremely crucial role in the evolution of renal fibrosis....
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BMC
2022-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-021-01122-w |
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| author | Mengling Wang Feng Zeng Fengling Ning Yinhang Wang Shilin Zhou Jiaqi He Cong Li Cong Wang Xiaolin Sun Dongliang Zhang Jisheng Xiao Ping Hu Svetlana Reilly Hong Xin Xudong Xu Xuemei Zhang |
| author_facet | Mengling Wang Feng Zeng Fengling Ning Yinhang Wang Shilin Zhou Jiaqi He Cong Li Cong Wang Xiaolin Sun Dongliang Zhang Jisheng Xiao Ping Hu Svetlana Reilly Hong Xin Xudong Xu Xuemei Zhang |
| author_sort | Mengling Wang |
| collection | DOAJ |
| description | 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 |
| format | Article |
| id | doaj-art-c554d5ee1626454fbb593a3ecbc911ec |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-c554d5ee1626454fbb593a3ecbc911ec2025-02-02T12:41:19ZengBMCJournal of Nanobiotechnology1477-31552022-01-0120111810.1186/s12951-021-01122-wCeria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysisMengling Wang0Feng Zeng1Fengling Ning2Yinhang Wang3Shilin Zhou4Jiaqi He5Cong Li6Cong Wang7Xiaolin Sun8Dongliang Zhang9Jisheng Xiao10Ping Hu11Svetlana Reilly12Hong Xin13Xudong Xu14Xuemei Zhang15Department of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan UniversityArtemisinin Research Center, Institute of Science and Technology, The First Clinical Medical School, Lingnan Medical Research Center, The First Affiliated Hospital, Guangzhou University of Chinese MedicineDepartment of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan UniversityDepartment of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan UniversityDepartment of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan UniversityDepartment of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan UniversityDepartment of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan UniversityKey Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China, Academy for Engineering and Technology, Fudan UniversityDepartment of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan UniversityDepartment of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan UniversityScience and Technology Innovation Center, Guangzhou University of Chinese MedicineDepartment of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan UniversityDivision of Cardiovascular Medicine, Department of Medicine, University of Oxford, John Radcliffe HospitalDepartment of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan UniversityDepartment of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan UniversityDepartment of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan UniversityAbstract 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 Abstracthttps://doi.org/10.1186/s12951-021-01122-wCeria nanoparticlesMetabolic reprogrammingOxidative phosphorylationAerobic glycolysisRenal fibrosis |
| spellingShingle | Mengling Wang Feng Zeng Fengling Ning Yinhang Wang Shilin Zhou Jiaqi He Cong Li Cong Wang Xiaolin Sun Dongliang Zhang Jisheng Xiao Ping Hu Svetlana Reilly Hong Xin Xudong Xu Xuemei Zhang Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis Journal of Nanobiotechnology Ceria nanoparticles Metabolic reprogramming Oxidative phosphorylation Aerobic glycolysis Renal fibrosis |
| title | Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis |
| title_full | Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis |
| title_fullStr | Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis |
| title_full_unstemmed | Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis |
| title_short | Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis |
| title_sort | ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis |
| topic | Ceria nanoparticles Metabolic reprogramming Oxidative phosphorylation Aerobic glycolysis Renal fibrosis |
| url | https://doi.org/10.1186/s12951-021-01122-w |
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