Tubular MYDGF Slows Progression of Chronic Kidney Disease by Maintaining Mitochondrial Homeostasis
Abstract Mitochondrial dysfunction is a key event driving the maladaptive repair of tubular epithelial cells during the transition from acute kidney injury to chronic kidney disease (CKD). Therefore, identifying potential targets involved in mitochondrial dysfunction in tubular epithelial cells is c...
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| Format: | Article |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409756 |
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| author | Xiaohan Liu Yang Zhang Youzhao Wang Yujie Yang Zhe Qiao Ping Zhan Huiying Jin Qianqian Xu Wei Tang Yu Sun Yan Zhang Fan Yi Min Liu |
| author_facet | Xiaohan Liu Yang Zhang Youzhao Wang Yujie Yang Zhe Qiao Ping Zhan Huiying Jin Qianqian Xu Wei Tang Yu Sun Yan Zhang Fan Yi Min Liu |
| author_sort | Xiaohan Liu |
| collection | DOAJ |
| description | Abstract Mitochondrial dysfunction is a key event driving the maladaptive repair of tubular epithelial cells during the transition from acute kidney injury to chronic kidney disease (CKD). Therefore, identifying potential targets involved in mitochondrial dysfunction in tubular epithelial cells is clinically important. Myeloid‐derived growth factor (MYDGF), a novel secreted protein, plays important roles in multiple cardiovascular diseases, but the function of MYDGF in tubular epithelial cells remains unknown. In the present study, it is found that MYDGF expression is significantly reduced in the cortex of the kidney, especially in the proximal tubules, from mice with CKD. Notably, lower expression of MYDGF is observed in tubules from patients with CKD and the level of MYDGF correlated with key factors related to kidney fibrosis and estimated glomerular filtration rate (eGFR) in patients with CKD. Tubule‐specific deletion of Mydgf exacerbates kidney injury in mice with CKD; however, Mydgf overexpression attenuates kidney fibrosis by remodeling mitochondrial homeostasis in tubular epithelial cells. Mechanistically, renal tubular MYDGF positively regulates the expression of isocitrate dehydrogenase 2 (IDH2), restores mitochondrial homeostasis, and slows CKD progression. Thus, this study indicates that MYDGF derived from tubules may be an effective therapeutic strategy for patients with CKD. |
| format | Article |
| id | doaj-art-2d71cf3881d54817885308d7a5a0a7c2 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-2d71cf3881d54817885308d7a5a0a7c22025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202409756Tubular MYDGF Slows Progression of Chronic Kidney Disease by Maintaining Mitochondrial HomeostasisXiaohan Liu0Yang Zhang1Youzhao Wang2Yujie Yang3Zhe Qiao4Ping Zhan5Huiying Jin6Qianqian Xu7Wei Tang8Yu Sun9Yan Zhang10Fan Yi11Min Liu12Department of Pharmacology School of Basic Medical Sciences Shandong University Jinan 250012 ChinaDepartment of Pharmacy The Second Hospital Cheeloo College of Medicine Shandong University Jinan 250033 ChinaDepartment of Pharmacology School of Basic Medical Sciences Shandong University Jinan 250012 ChinaDepartment of Pharmacology School of Basic Medical Sciences Shandong University Jinan 250012 ChinaDepartment of Pharmacology School of Basic Medical Sciences Shandong University Jinan 250012 ChinaDepartment of Pharmacology School of Basic Medical Sciences Shandong University Jinan 250012 ChinaDepartment of Pharmacology School of Basic Medical Sciences Shandong University Jinan 250012 ChinaDepartment of Organ Transplantation Qilu Hospital of Shandong University Jinan 250012 ChinaDepartment of Pharmacology School of Basic Medical Sciences Shandong University Jinan 250012 ChinaDepartment of Pharmacology School of Basic Medical Sciences Shandong University Jinan 250012 ChinaDepartment of Pharmacology School of Basic Medical Sciences Shandong University Jinan 250012 ChinaDepartment of Pharmacology School of Basic Medical Sciences Shandong University Jinan 250012 ChinaDepartment of Pharmacology School of Basic Medical Sciences Shandong University Jinan 250012 ChinaAbstract Mitochondrial dysfunction is a key event driving the maladaptive repair of tubular epithelial cells during the transition from acute kidney injury to chronic kidney disease (CKD). Therefore, identifying potential targets involved in mitochondrial dysfunction in tubular epithelial cells is clinically important. Myeloid‐derived growth factor (MYDGF), a novel secreted protein, plays important roles in multiple cardiovascular diseases, but the function of MYDGF in tubular epithelial cells remains unknown. In the present study, it is found that MYDGF expression is significantly reduced in the cortex of the kidney, especially in the proximal tubules, from mice with CKD. Notably, lower expression of MYDGF is observed in tubules from patients with CKD and the level of MYDGF correlated with key factors related to kidney fibrosis and estimated glomerular filtration rate (eGFR) in patients with CKD. Tubule‐specific deletion of Mydgf exacerbates kidney injury in mice with CKD; however, Mydgf overexpression attenuates kidney fibrosis by remodeling mitochondrial homeostasis in tubular epithelial cells. Mechanistically, renal tubular MYDGF positively regulates the expression of isocitrate dehydrogenase 2 (IDH2), restores mitochondrial homeostasis, and slows CKD progression. Thus, this study indicates that MYDGF derived from tubules may be an effective therapeutic strategy for patients with CKD.https://doi.org/10.1002/advs.202409756chronic kidney diseasemitochondrial homeostasisMYDGFtubular epithelial cells |
| spellingShingle | Xiaohan Liu Yang Zhang Youzhao Wang Yujie Yang Zhe Qiao Ping Zhan Huiying Jin Qianqian Xu Wei Tang Yu Sun Yan Zhang Fan Yi Min Liu Tubular MYDGF Slows Progression of Chronic Kidney Disease by Maintaining Mitochondrial Homeostasis Advanced Science chronic kidney disease mitochondrial homeostasis MYDGF tubular epithelial cells |
| title | Tubular MYDGF Slows Progression of Chronic Kidney Disease by Maintaining Mitochondrial Homeostasis |
| title_full | Tubular MYDGF Slows Progression of Chronic Kidney Disease by Maintaining Mitochondrial Homeostasis |
| title_fullStr | Tubular MYDGF Slows Progression of Chronic Kidney Disease by Maintaining Mitochondrial Homeostasis |
| title_full_unstemmed | Tubular MYDGF Slows Progression of Chronic Kidney Disease by Maintaining Mitochondrial Homeostasis |
| title_short | Tubular MYDGF Slows Progression of Chronic Kidney Disease by Maintaining Mitochondrial Homeostasis |
| title_sort | tubular mydgf slows progression of chronic kidney disease by maintaining mitochondrial homeostasis |
| topic | chronic kidney disease mitochondrial homeostasis MYDGF tubular epithelial cells |
| url | https://doi.org/10.1002/advs.202409756 |
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