IL‐22‐mediated renal metabolic reprogramming via PFKFB3 to treat kidney injury
Abstract Kidney damage initiates the deteriorating metabolic states in tubule cells that lead to the development of end‐stage renal disease (ESTD). Interleukin‐22 (IL‐22) is an effective therapeutic antidote for kidney injury via promoting kidney recovery, but little is known about the underlying mo...
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| Format: | Article |
| Language: | English |
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Wiley
2021-02-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.324 |
| _version_ | 1797894354960908288 |
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| author | Wei Chen Yilan Shen Jiajun Fan Xian Zeng Xuyao Zhang Jingyun Luan Yichen Wang Jinghui Zhang Si Fang Xiaobin Mei Zhen Zhao Dianwen Ju |
| author_facet | Wei Chen Yilan Shen Jiajun Fan Xian Zeng Xuyao Zhang Jingyun Luan Yichen Wang Jinghui Zhang Si Fang Xiaobin Mei Zhen Zhao Dianwen Ju |
| author_sort | Wei Chen |
| collection | DOAJ |
| description | Abstract Kidney damage initiates the deteriorating metabolic states in tubule cells that lead to the development of end‐stage renal disease (ESTD). Interleukin‐22 (IL‐22) is an effective therapeutic antidote for kidney injury via promoting kidney recovery, but little is known about the underlying molecular mechanisms. Here, we first provide evidence that IL‐22 attenuates kidney injury via metabolic reprogramming of renal tubular epithelial cells (TECs). Specifically, our data suggest that IL‐22 regulates mitochondrial function and glycolysis in damaged TECs. Further observations indicate that IL‐22 alleviates the accumulation of mitochondrial reactive oxygen species (ROS) and dysfunctional mitochondria via the induction of AMPK/AKT signaling and PFBFK3 activities. In mice, amelioration of kidney injury and necrosis and improvement of kidney functions via regulation of these metabolism relevant signaling and mitochondrial fitness of recombinant IL‐22 are certificated in cisplatin‐induced kidney damage and diabetic nephropathy (DN) animal models. Taken together, our findings unravel new mechanistic insights into protective effects of IL‐22 on kidneys and highlight the therapeutic opportunities of IL‐22 and the involved metabolic regulators in various kidney diseases. |
| first_indexed | 2024-04-10T07:08:45Z |
| format | Article |
| id | doaj.art-bf9b9a4e7c534c9b80aa0fe378121b0b |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-04-10T07:08:45Z |
| publishDate | 2021-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj.art-bf9b9a4e7c534c9b80aa0fe378121b0b2023-02-27T05:10:47ZengWileyClinical and Translational Medicine2001-13262021-02-01112n/an/a10.1002/ctm2.324IL‐22‐mediated renal metabolic reprogramming via PFKFB3 to treat kidney injuryWei Chen0Yilan Shen1Jiajun Fan2Xian Zeng3Xuyao Zhang4Jingyun Luan5Yichen Wang6Jinghui Zhang7Si Fang8Xiaobin Mei9Zhen Zhao10Dianwen Ju11School of Pharmacy and Minhang Hospital Shanghai Engineering Research Center of Immunotherapeutics Fudan University Shanghai P. R. ChinaSchool of Pharmacy and Minhang Hospital Shanghai Engineering Research Center of Immunotherapeutics Fudan University Shanghai P. R. ChinaSchool of Pharmacy and Minhang Hospital Shanghai Engineering Research Center of Immunotherapeutics Fudan University Shanghai P. R. ChinaSchool of Pharmacy and Minhang Hospital Shanghai Engineering Research Center of Immunotherapeutics Fudan University Shanghai P. R. ChinaSchool of Pharmacy and Minhang Hospital Shanghai Engineering Research Center of Immunotherapeutics Fudan University Shanghai P. R. ChinaSchool of Pharmacy and Minhang Hospital Shanghai Engineering Research Center of Immunotherapeutics Fudan University Shanghai P. R. ChinaSchool of Pharmacy and Minhang Hospital Shanghai Engineering Research Center of Immunotherapeutics Fudan University Shanghai P. R. ChinaSchool of Pharmacy and Minhang Hospital Shanghai Engineering Research Center of Immunotherapeutics Fudan University Shanghai P. R. ChinaTongcheng Hospital of Traditional Chinese Medicine Anhui P. R. ChinaChanghai Hospital Second Military Medical University Shanghai P. R. ChinaSchool of Pharmacy and Minhang Hospital Shanghai Engineering Research Center of Immunotherapeutics Fudan University Shanghai P. R. ChinaSchool of Pharmacy and Minhang Hospital Shanghai Engineering Research Center of Immunotherapeutics Fudan University Shanghai P. R. ChinaAbstract Kidney damage initiates the deteriorating metabolic states in tubule cells that lead to the development of end‐stage renal disease (ESTD). Interleukin‐22 (IL‐22) is an effective therapeutic antidote for kidney injury via promoting kidney recovery, but little is known about the underlying molecular mechanisms. Here, we first provide evidence that IL‐22 attenuates kidney injury via metabolic reprogramming of renal tubular epithelial cells (TECs). Specifically, our data suggest that IL‐22 regulates mitochondrial function and glycolysis in damaged TECs. Further observations indicate that IL‐22 alleviates the accumulation of mitochondrial reactive oxygen species (ROS) and dysfunctional mitochondria via the induction of AMPK/AKT signaling and PFBFK3 activities. In mice, amelioration of kidney injury and necrosis and improvement of kidney functions via regulation of these metabolism relevant signaling and mitochondrial fitness of recombinant IL‐22 are certificated in cisplatin‐induced kidney damage and diabetic nephropathy (DN) animal models. Taken together, our findings unravel new mechanistic insights into protective effects of IL‐22 on kidneys and highlight the therapeutic opportunities of IL‐22 and the involved metabolic regulators in various kidney diseases.https://doi.org/10.1002/ctm2.324interleukin‐22kidney injurymetabolic reprogrammingmitochondrial dysfunction |
| spellingShingle | Wei Chen Yilan Shen Jiajun Fan Xian Zeng Xuyao Zhang Jingyun Luan Yichen Wang Jinghui Zhang Si Fang Xiaobin Mei Zhen Zhao Dianwen Ju IL‐22‐mediated renal metabolic reprogramming via PFKFB3 to treat kidney injury Clinical and Translational Medicine interleukin‐22 kidney injury metabolic reprogramming mitochondrial dysfunction |
| title | IL‐22‐mediated renal metabolic reprogramming via PFKFB3 to treat kidney injury |
| title_full | IL‐22‐mediated renal metabolic reprogramming via PFKFB3 to treat kidney injury |
| title_fullStr | IL‐22‐mediated renal metabolic reprogramming via PFKFB3 to treat kidney injury |
| title_full_unstemmed | IL‐22‐mediated renal metabolic reprogramming via PFKFB3 to treat kidney injury |
| title_short | IL‐22‐mediated renal metabolic reprogramming via PFKFB3 to treat kidney injury |
| title_sort | il 22 mediated renal metabolic reprogramming via pfkfb3 to treat kidney injury |
| topic | interleukin‐22 kidney injury metabolic reprogramming mitochondrial dysfunction |
| url | https://doi.org/10.1002/ctm2.324 |
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