Uncoupling protein 1 inhibits mitochondrial reactive oxygen species generation and alleviates acute kidney injury
Background: Uncoupling protein 1 (UCP1) is predominantly found in brown adipose tissue mitochondria, and mediates energy dissipation to generate heat rather than ATP via functional mitochondrial uncoupling. However, little is known about its expression and function in kidney. Methods: We carried out...
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| Format: | Article |
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Elsevier
2019-11-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419306875 |
| _version_ | 1818955386458210304 |
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| author | Ping Jia Xiaoli Wu Tianyi Pan Sujuan Xu Jiachang Hu Xiaoqiang Ding |
| author_facet | Ping Jia Xiaoli Wu Tianyi Pan Sujuan Xu Jiachang Hu Xiaoqiang Ding |
| author_sort | Ping Jia |
| collection | DOAJ |
| description | Background: Uncoupling protein 1 (UCP1) is predominantly found in brown adipose tissue mitochondria, and mediates energy dissipation to generate heat rather than ATP via functional mitochondrial uncoupling. However, little is known about its expression and function in kidney. Methods: We carried out a mRNA microarray analysis in mice kidneys with ischemia reperfusion (IR) injury. The most dramatically downregulated gene UCP1 after IR was identified, and its role in generation of mitochondrial reactive oxygen species (ROS) and oxidative stress injury was assessed both in vitro and in vivo. Genetic deletion of UCP1 was used to investigate the effects of UCP1 on ischemia or cisplatin-indued acute kidney injury (AKI) in mice. Findings: UCP1 was located in renal tubular epithelial cells in kidney and downregulated in a time-dependent manner during renal IR. Deletion of UCP1 increased oxidative stress in kidneys and aggravated ischemia or cisplatin induced AKI in mice.Viral-based overexpression of UCP1 reduced mitochondrial ROS generation and apoptosis in hypoxia-treated tubular epithelial cells. Furthermore, UCP1 expression was regulated by peroxisome proliferator-activator receptor (PPAR) γ in kidneys during renal IR. Overexpression of PPAR-γ resembled UCP1-overexpression phenotype in vitro. Treatment with PPAR-γ agonist could induce UCP1 upregulation and provide protective effect against renal IR injury in UCP1+/+mice, but not in UCP1−/−mice. Interpretation: UCP1 protects against AKI likely by suppressing oxidative stress, and activation of UCP1 represents a potential therapeutic strategy for AKI. Fund: National Natural Science Foundation of China grants, Science and Technology Commission of Shanghai. Keywords: Acute kidney injury, Uncoupling protein 1, Reactive oxygen species, Peroxisome proliferator-activator receptor γ |
| first_indexed | 2024-12-20T10:37:14Z |
| format | Article |
| id | doaj.art-4d8d4358e22141ec8e48f5d0a9324255 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-20T10:37:14Z |
| publishDate | 2019-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-4d8d4358e22141ec8e48f5d0a93242552022-12-21T19:43:37ZengElsevierEBioMedicine2352-39642019-11-0149331340Uncoupling protein 1 inhibits mitochondrial reactive oxygen species generation and alleviates acute kidney injuryPing Jia0Xiaoli Wu1Tianyi Pan2Sujuan Xu3Jiachang Hu4Xiaoqiang Ding5Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Kidney and Blood Purification Laboratory of Shanghai, Shanghai, ChinaTraditional Chinese Medicine Pharmacology Laboratory, Longhua Hospital, Shanghai University of Tranditional Chinese Medicine, Shanghai, ChinaDivision of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDivision of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDivision of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDivision of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Medical Center of Kidney, Shanghai, China; Kidney and Dialysis Institute of Shanghai, Shanghai, China; Kidney and Blood Purification Laboratory of Shanghai, Shanghai, China; Hemodialysis quality control center of Shanghai, Shanghai, China; Corresponding author at: Division of Nephrology, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, Shanghai 200032, China.Background: Uncoupling protein 1 (UCP1) is predominantly found in brown adipose tissue mitochondria, and mediates energy dissipation to generate heat rather than ATP via functional mitochondrial uncoupling. However, little is known about its expression and function in kidney. Methods: We carried out a mRNA microarray analysis in mice kidneys with ischemia reperfusion (IR) injury. The most dramatically downregulated gene UCP1 after IR was identified, and its role in generation of mitochondrial reactive oxygen species (ROS) and oxidative stress injury was assessed both in vitro and in vivo. Genetic deletion of UCP1 was used to investigate the effects of UCP1 on ischemia or cisplatin-indued acute kidney injury (AKI) in mice. Findings: UCP1 was located in renal tubular epithelial cells in kidney and downregulated in a time-dependent manner during renal IR. Deletion of UCP1 increased oxidative stress in kidneys and aggravated ischemia or cisplatin induced AKI in mice.Viral-based overexpression of UCP1 reduced mitochondrial ROS generation and apoptosis in hypoxia-treated tubular epithelial cells. Furthermore, UCP1 expression was regulated by peroxisome proliferator-activator receptor (PPAR) γ in kidneys during renal IR. Overexpression of PPAR-γ resembled UCP1-overexpression phenotype in vitro. Treatment with PPAR-γ agonist could induce UCP1 upregulation and provide protective effect against renal IR injury in UCP1+/+mice, but not in UCP1−/−mice. Interpretation: UCP1 protects against AKI likely by suppressing oxidative stress, and activation of UCP1 represents a potential therapeutic strategy for AKI. Fund: National Natural Science Foundation of China grants, Science and Technology Commission of Shanghai. Keywords: Acute kidney injury, Uncoupling protein 1, Reactive oxygen species, Peroxisome proliferator-activator receptor γhttp://www.sciencedirect.com/science/article/pii/S2352396419306875 |
| spellingShingle | Ping Jia Xiaoli Wu Tianyi Pan Sujuan Xu Jiachang Hu Xiaoqiang Ding Uncoupling protein 1 inhibits mitochondrial reactive oxygen species generation and alleviates acute kidney injury EBioMedicine |
| title | Uncoupling protein 1 inhibits mitochondrial reactive oxygen species generation and alleviates acute kidney injury |
| title_full | Uncoupling protein 1 inhibits mitochondrial reactive oxygen species generation and alleviates acute kidney injury |
| title_fullStr | Uncoupling protein 1 inhibits mitochondrial reactive oxygen species generation and alleviates acute kidney injury |
| title_full_unstemmed | Uncoupling protein 1 inhibits mitochondrial reactive oxygen species generation and alleviates acute kidney injury |
| title_short | Uncoupling protein 1 inhibits mitochondrial reactive oxygen species generation and alleviates acute kidney injury |
| title_sort | uncoupling protein 1 inhibits mitochondrial reactive oxygen species generation and alleviates acute kidney injury |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419306875 |
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