Overexpression of miR-92a attenuates kidney ischemia–reperfusion injury and improves kidney preservation by inhibiting MEK4/JNK1-related autophagy
Abstract Background Kidney ischemia–reperfusion injury is inevitable in kidney transplantation, and is essential for primary graft dysfunction and delayed graft function. Our previous study has proved that miR-92a could ameliorate kidney ischemia–reperfusion injury, but the mechanism has not been st...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Cellular & Molecular Biology Letters |
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| Online Access: | https://doi.org/10.1186/s11658-023-00430-3 |
| _version_ | 1827983331275309056 |
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| author | Ming Ma Hui Li Saifu Yin Tao Lin Turun Song |
| author_facet | Ming Ma Hui Li Saifu Yin Tao Lin Turun Song |
| author_sort | Ming Ma |
| collection | DOAJ |
| description | Abstract Background Kidney ischemia–reperfusion injury is inevitable in kidney transplantation, and is essential for primary graft dysfunction and delayed graft function. Our previous study has proved that miR-92a could ameliorate kidney ischemia–reperfusion injury, but the mechanism has not been studied. Methods This study conducted further research on the role of miR-92a in kidney ischemia–reperfusion injury and organ preservation. In vivo, mice models of bilateral kidney ischemia (30 min), cold preservation after ischemia (cold preservation time of 6, 12, and 24 h), and ischemia–reperfusion (reperfusion time of 24, 48, and 72 h) were established. Before or after modeling, the model mice were injected with miR-92a-agomir through the caudal vein. In vitro, the hypoxia–reoxygenation of HK-2 cells was used to simulate ischemia–reperfusion injury. Results Kidney ischemia and ischemia–reperfusion significantly damaged kidney function, decreased the expression of miR-92a, and increased apoptosis and autophagy in kidneys. miR-92a agomir tail vein injection significantly increased the expression of miR-92a in kidneys, improved kidney function, and alleviated kidney injury, and the intervention before modeling achieved a better effect than after. Moreover, miR-92a agomir significantly reduced the apoptosis and autophagy in HK-2 cells induced by hypoxia, hypoxia–reoxygenation, and rapamycin, while miR-92a antagomir had opposite effects. Furthermore, mitogen-activated protein kinase, c-Jun NH (2) terminal kinase, caspase 3, Beclin 1, and microtubule-associated protein 1 light chain 3B were inhibited by overexpression of miR-92a both in vivo and in vitro, which in turn reduced apoptosis and autophagy. Conclusions Our results prove that overexpression of miR-92a attenuated kidney ischemia–reperfusion injury and improved kidney preservation, and intervention before ischemia–reperfusion provides better protection than after. |
| first_indexed | 2024-04-09T22:45:53Z |
| format | Article |
| id | doaj.art-676f3d1a1c4742c8a952f121b8e41ddc |
| institution | Directory Open Access Journal |
| issn | 1689-1392 |
| language | English |
| last_indexed | 2024-04-09T22:45:53Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cellular & Molecular Biology Letters |
| spelling | doaj.art-676f3d1a1c4742c8a952f121b8e41ddc2023-03-22T11:49:58ZengBMCCellular & Molecular Biology Letters1689-13922023-03-0128111410.1186/s11658-023-00430-3Overexpression of miR-92a attenuates kidney ischemia–reperfusion injury and improves kidney preservation by inhibiting MEK4/JNK1-related autophagyMing Ma0Hui Li1Saifu Yin2Tao Lin3Turun Song4Department of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, West China Hospital, Sichuan UniversityAbstract Background Kidney ischemia–reperfusion injury is inevitable in kidney transplantation, and is essential for primary graft dysfunction and delayed graft function. Our previous study has proved that miR-92a could ameliorate kidney ischemia–reperfusion injury, but the mechanism has not been studied. Methods This study conducted further research on the role of miR-92a in kidney ischemia–reperfusion injury and organ preservation. In vivo, mice models of bilateral kidney ischemia (30 min), cold preservation after ischemia (cold preservation time of 6, 12, and 24 h), and ischemia–reperfusion (reperfusion time of 24, 48, and 72 h) were established. Before or after modeling, the model mice were injected with miR-92a-agomir through the caudal vein. In vitro, the hypoxia–reoxygenation of HK-2 cells was used to simulate ischemia–reperfusion injury. Results Kidney ischemia and ischemia–reperfusion significantly damaged kidney function, decreased the expression of miR-92a, and increased apoptosis and autophagy in kidneys. miR-92a agomir tail vein injection significantly increased the expression of miR-92a in kidneys, improved kidney function, and alleviated kidney injury, and the intervention before modeling achieved a better effect than after. Moreover, miR-92a agomir significantly reduced the apoptosis and autophagy in HK-2 cells induced by hypoxia, hypoxia–reoxygenation, and rapamycin, while miR-92a antagomir had opposite effects. Furthermore, mitogen-activated protein kinase, c-Jun NH (2) terminal kinase, caspase 3, Beclin 1, and microtubule-associated protein 1 light chain 3B were inhibited by overexpression of miR-92a both in vivo and in vitro, which in turn reduced apoptosis and autophagy. Conclusions Our results prove that overexpression of miR-92a attenuated kidney ischemia–reperfusion injury and improved kidney preservation, and intervention before ischemia–reperfusion provides better protection than after.https://doi.org/10.1186/s11658-023-00430-3miR-92aKidney transplantIschemia–reperfusion injuryAutophagyApoptosis |
| spellingShingle | Ming Ma Hui Li Saifu Yin Tao Lin Turun Song Overexpression of miR-92a attenuates kidney ischemia–reperfusion injury and improves kidney preservation by inhibiting MEK4/JNK1-related autophagy Cellular & Molecular Biology Letters miR-92a Kidney transplant Ischemia–reperfusion injury Autophagy Apoptosis |
| title | Overexpression of miR-92a attenuates kidney ischemia–reperfusion injury and improves kidney preservation by inhibiting MEK4/JNK1-related autophagy |
| title_full | Overexpression of miR-92a attenuates kidney ischemia–reperfusion injury and improves kidney preservation by inhibiting MEK4/JNK1-related autophagy |
| title_fullStr | Overexpression of miR-92a attenuates kidney ischemia–reperfusion injury and improves kidney preservation by inhibiting MEK4/JNK1-related autophagy |
| title_full_unstemmed | Overexpression of miR-92a attenuates kidney ischemia–reperfusion injury and improves kidney preservation by inhibiting MEK4/JNK1-related autophagy |
| title_short | Overexpression of miR-92a attenuates kidney ischemia–reperfusion injury and improves kidney preservation by inhibiting MEK4/JNK1-related autophagy |
| title_sort | overexpression of mir 92a attenuates kidney ischemia reperfusion injury and improves kidney preservation by inhibiting mek4 jnk1 related autophagy |
| topic | miR-92a Kidney transplant Ischemia–reperfusion injury Autophagy Apoptosis |
| url | https://doi.org/10.1186/s11658-023-00430-3 |
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