Circadian gene BMAL1 ameliorates renal ischaemia-reperfusion injury in diabetic mice by enhancing mitophagy via the HIF-1/BNIP3 pathway
Abstract Diabetic kidneys are particularly vulnerable to ischemia/reperfusion injury (I/RI). Although previous research has suggested that the circadian gene brain and muscle ARNT-like 1 (BMAL1) plays a role in regulating renal function, the exact functions and mechanisms of BMAL1 in diabetic renal...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-03515-5 |
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| author | Xinqi Deng Yan Leng Yonghong Xiong Wenyuan Li Wu Chen Yuhang Yang Bihan Wang Siyuan Gong Yunhao Wang Baichuan Yang Wei Li |
| author_facet | Xinqi Deng Yan Leng Yonghong Xiong Wenyuan Li Wu Chen Yuhang Yang Bihan Wang Siyuan Gong Yunhao Wang Baichuan Yang Wei Li |
| author_sort | Xinqi Deng |
| collection | DOAJ |
| description | Abstract Diabetic kidneys are particularly vulnerable to ischemia/reperfusion injury (I/RI). Although previous research has suggested that the circadian gene brain and muscle ARNT-like 1 (BMAL1) plays a role in regulating renal function, the exact functions and mechanisms of BMAL1 in diabetic renal I/RI remain elusive. In this study, bilateral renal artery ligation and release were performed in non-diabetic (db/+) and diabetic (db/db) mice. In diabetic kidneys, experimental findings demonstrated a significant decrease in BMAL1 expression, along with the inhibition of the HIF-1α/BNIP3 signaling pathway and compromised mitophagy. BMAL1 overexpression alleviated cell damage and apoptosis under high glucose and hypoxia/reoxygenation stimulation. Inhibition of the Hypoxia-inducible factor-1α (HIF-1α)/ B-cell lymphoma-2 interacting protein 3 (BNIP3) pathway by the HIF-1α inhibitor PX-478 intensified cellular damage and reduced the protective effect of BMAL1 overexpression in TCMK-1 cells. These results indicate that BMAL1 regulates mitophagy in diabetic renal I/RI through the HIF-1α/BNIP3 pathway, providing valuable insights for the development of targeted therapies for diabetic renal I/RI. |
| format | Article |
| id | doaj-art-b0155da58d2048d681fb94355f61bd38 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
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| series | Scientific Reports |
| spelling | doaj-art-b0155da58d2048d681fb94355f61bd382025-08-20T03:45:35ZengNature PortfolioScientific Reports2045-23222025-07-0115111710.1038/s41598-025-03515-5Circadian gene BMAL1 ameliorates renal ischaemia-reperfusion injury in diabetic mice by enhancing mitophagy via the HIF-1/BNIP3 pathwayXinqi Deng0Yan Leng1Yonghong Xiong2Wenyuan Li3Wu Chen4Yuhang Yang5Bihan Wang6Siyuan Gong7Yunhao Wang8Baichuan Yang9Wei Li10Department of Anesthesiology, Renmin Hospital of Wuhan UniversityDepartment of Anesthesiology, Renmin Hospital of Wuhan UniversityDepartment of Anesthesiology, Renmin Hospital of Wuhan UniversityDepartment of Anesthesiology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Anesthesiology, Renmin Hospital of Wuhan UniversityDepartment of Anesthesiology, Renmin Hospital of Wuhan UniversityDepartment of Anesthesiology, Renmin Hospital of Wuhan UniversityDepartment of Anesthesiology, Renmin Hospital of Wuhan UniversityDepartment of Anesthesiology, Renmin Hospital of Wuhan UniversityDepartment of Anesthesiology, Renmin Hospital of Wuhan UniversityAbstract Diabetic kidneys are particularly vulnerable to ischemia/reperfusion injury (I/RI). Although previous research has suggested that the circadian gene brain and muscle ARNT-like 1 (BMAL1) plays a role in regulating renal function, the exact functions and mechanisms of BMAL1 in diabetic renal I/RI remain elusive. In this study, bilateral renal artery ligation and release were performed in non-diabetic (db/+) and diabetic (db/db) mice. In diabetic kidneys, experimental findings demonstrated a significant decrease in BMAL1 expression, along with the inhibition of the HIF-1α/BNIP3 signaling pathway and compromised mitophagy. BMAL1 overexpression alleviated cell damage and apoptosis under high glucose and hypoxia/reoxygenation stimulation. Inhibition of the Hypoxia-inducible factor-1α (HIF-1α)/ B-cell lymphoma-2 interacting protein 3 (BNIP3) pathway by the HIF-1α inhibitor PX-478 intensified cellular damage and reduced the protective effect of BMAL1 overexpression in TCMK-1 cells. These results indicate that BMAL1 regulates mitophagy in diabetic renal I/RI through the HIF-1α/BNIP3 pathway, providing valuable insights for the development of targeted therapies for diabetic renal I/RI.https://doi.org/10.1038/s41598-025-03515-5BMAL1DiabetesHIF-1αIschemia/reperfusion injuryMitophagy |
| spellingShingle | Xinqi Deng Yan Leng Yonghong Xiong Wenyuan Li Wu Chen Yuhang Yang Bihan Wang Siyuan Gong Yunhao Wang Baichuan Yang Wei Li Circadian gene BMAL1 ameliorates renal ischaemia-reperfusion injury in diabetic mice by enhancing mitophagy via the HIF-1/BNIP3 pathway Scientific Reports BMAL1 Diabetes HIF-1α Ischemia/reperfusion injury Mitophagy |
| title | Circadian gene BMAL1 ameliorates renal ischaemia-reperfusion injury in diabetic mice by enhancing mitophagy via the HIF-1/BNIP3 pathway |
| title_full | Circadian gene BMAL1 ameliorates renal ischaemia-reperfusion injury in diabetic mice by enhancing mitophagy via the HIF-1/BNIP3 pathway |
| title_fullStr | Circadian gene BMAL1 ameliorates renal ischaemia-reperfusion injury in diabetic mice by enhancing mitophagy via the HIF-1/BNIP3 pathway |
| title_full_unstemmed | Circadian gene BMAL1 ameliorates renal ischaemia-reperfusion injury in diabetic mice by enhancing mitophagy via the HIF-1/BNIP3 pathway |
| title_short | Circadian gene BMAL1 ameliorates renal ischaemia-reperfusion injury in diabetic mice by enhancing mitophagy via the HIF-1/BNIP3 pathway |
| title_sort | circadian gene bmal1 ameliorates renal ischaemia reperfusion injury in diabetic mice by enhancing mitophagy via the hif 1 bnip3 pathway |
| topic | BMAL1 Diabetes HIF-1α Ischemia/reperfusion injury Mitophagy |
| url | https://doi.org/10.1038/s41598-025-03515-5 |
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