UCP1 alleviates renal interstitial fibrosis progression through oxidative stress pathway mediated by SIRT3 protein stability
Abstract Background Renal interstitial fibrosis is a common pathway for the progressive development of chronic renal diseases (CKD) with different etiology, and is the main pathological basis leading to end-stage renal disease. Although the current research on renal interstitial fibrosis is graduall...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-023-04376-0 |
| _version_ | 1797752628629733376 |
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| author | Wei Xiong Zhiyong Xiong Anni Song Chuntao Lei Chen Ye Hua Su Chun Zhang |
| author_facet | Wei Xiong Zhiyong Xiong Anni Song Chuntao Lei Chen Ye Hua Su Chun Zhang |
| author_sort | Wei Xiong |
| collection | DOAJ |
| description | Abstract Background Renal interstitial fibrosis is a common pathway for the progressive development of chronic renal diseases (CKD) with different etiology, and is the main pathological basis leading to end-stage renal disease. Although the current research on renal interstitial fibrosis is gradually deepening, the diagnosis and treatment methods are still very lacking. Uncoupling protein 1 (UCP1) is a nuclear encoded protein in mitochondria inner membrane and plays an important role in regulating energy metabolism and mitochondrial homeostasis. However, the biological significance of UCP1 and potential regulatory mechanisms in the development of CKD remain unclear. Methods Unilateral ureteral obstruction (UUO) model was used to construct the animal model of renal fibrosis, and TGF-β1 stimulation of HK2 cells was used to construct the vitro model of renal fibrosis. UCP1 expression was detected by Western blot, immunoblot analysis and immunohistochemistry. UCP1 was upregulated by UCP1 overexpressing lentivirus and UCP1 agonist CL316243. Western blot and immunofluorescence were used to detect epithelial mesenchymal transition (EMT)-related markers, such as collagen I, fibronectin, antioxidant enzyme SOD2 and CAT. Reactive oxygen species (ROS) production was detected by ROS detection kit. SIRT3 knockdown was performed by siRNA. Results This study presents that UCP1 is significantly downregulated in patients with renal fibrosis and UUO model. Further studies discover that UCP1 overexpression and CL316243 treatments (UCP1 agonists) reversed EMT and extracellular matrix (ECM) accumulation in renal fibrosis models in vivo and in vitro. Simultaneously, UCP1 reduced the ROS production by increasing the stability of SIRT3. When SIRT3 was knocked down, the production of ROS decreased. Conclusions Elevating the expression of UCP1 can inhibit the occurrence of oxidative stress by stabilizing SIRT3, thereby reducing EMT and ECM accumulation, and ultimately alleviating renal interstitial fibrosis. It will provide new instructions and targets for the treatment of CKD. |
| first_indexed | 2024-03-12T17:07:16Z |
| format | Article |
| id | doaj.art-902867b6d0ef43d5814804f15a7c8c01 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-12T17:07:16Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-902867b6d0ef43d5814804f15a7c8c012023-08-06T11:23:34ZengBMCJournal of Translational Medicine1479-58762023-08-0121111710.1186/s12967-023-04376-0UCP1 alleviates renal interstitial fibrosis progression through oxidative stress pathway mediated by SIRT3 protein stabilityWei Xiong0Zhiyong Xiong1Anni Song2Chuntao Lei3Chen Ye4Hua Su5Chun Zhang6Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Renal interstitial fibrosis is a common pathway for the progressive development of chronic renal diseases (CKD) with different etiology, and is the main pathological basis leading to end-stage renal disease. Although the current research on renal interstitial fibrosis is gradually deepening, the diagnosis and treatment methods are still very lacking. Uncoupling protein 1 (UCP1) is a nuclear encoded protein in mitochondria inner membrane and plays an important role in regulating energy metabolism and mitochondrial homeostasis. However, the biological significance of UCP1 and potential regulatory mechanisms in the development of CKD remain unclear. Methods Unilateral ureteral obstruction (UUO) model was used to construct the animal model of renal fibrosis, and TGF-β1 stimulation of HK2 cells was used to construct the vitro model of renal fibrosis. UCP1 expression was detected by Western blot, immunoblot analysis and immunohistochemistry. UCP1 was upregulated by UCP1 overexpressing lentivirus and UCP1 agonist CL316243. Western blot and immunofluorescence were used to detect epithelial mesenchymal transition (EMT)-related markers, such as collagen I, fibronectin, antioxidant enzyme SOD2 and CAT. Reactive oxygen species (ROS) production was detected by ROS detection kit. SIRT3 knockdown was performed by siRNA. Results This study presents that UCP1 is significantly downregulated in patients with renal fibrosis and UUO model. Further studies discover that UCP1 overexpression and CL316243 treatments (UCP1 agonists) reversed EMT and extracellular matrix (ECM) accumulation in renal fibrosis models in vivo and in vitro. Simultaneously, UCP1 reduced the ROS production by increasing the stability of SIRT3. When SIRT3 was knocked down, the production of ROS decreased. Conclusions Elevating the expression of UCP1 can inhibit the occurrence of oxidative stress by stabilizing SIRT3, thereby reducing EMT and ECM accumulation, and ultimately alleviating renal interstitial fibrosis. It will provide new instructions and targets for the treatment of CKD.https://doi.org/10.1186/s12967-023-04376-0Renal interstitial fibrosisUCP1Reactive oxygen species (ROS)SIRT3Chronic kidney disease (CKD) |
| spellingShingle | Wei Xiong Zhiyong Xiong Anni Song Chuntao Lei Chen Ye Hua Su Chun Zhang UCP1 alleviates renal interstitial fibrosis progression through oxidative stress pathway mediated by SIRT3 protein stability Journal of Translational Medicine Renal interstitial fibrosis UCP1 Reactive oxygen species (ROS) SIRT3 Chronic kidney disease (CKD) |
| title | UCP1 alleviates renal interstitial fibrosis progression through oxidative stress pathway mediated by SIRT3 protein stability |
| title_full | UCP1 alleviates renal interstitial fibrosis progression through oxidative stress pathway mediated by SIRT3 protein stability |
| title_fullStr | UCP1 alleviates renal interstitial fibrosis progression through oxidative stress pathway mediated by SIRT3 protein stability |
| title_full_unstemmed | UCP1 alleviates renal interstitial fibrosis progression through oxidative stress pathway mediated by SIRT3 protein stability |
| title_short | UCP1 alleviates renal interstitial fibrosis progression through oxidative stress pathway mediated by SIRT3 protein stability |
| title_sort | ucp1 alleviates renal interstitial fibrosis progression through oxidative stress pathway mediated by sirt3 protein stability |
| topic | Renal interstitial fibrosis UCP1 Reactive oxygen species (ROS) SIRT3 Chronic kidney disease (CKD) |
| url | https://doi.org/10.1186/s12967-023-04376-0 |
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