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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-1\u03b1\/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-1\u03b1 (HIF-1\u03b1)\/ B-cell lymphoma-2 interacting protein 3 (BNIP3) pathway by the HIF-1\u03b1 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-1\u03b1\/BNIP3 pathway, providing valuable insights for the development of targeted therapies for diabetic renal I\/RI.<\/jats:p>","DOI":"10.1038\/s41598-025-03515-5","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T02:13:14Z","timestamp":1751422394000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Circadian gene BMAL1 ameliorates renal ischaemia-reperfusion injury in diabetic mice by enhancing mitophagy via the HIF-1\/BNIP3 pathway"],"prefix":"10.1038","volume":"15","author":[{"given":"Xinqi","family":"Deng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Leng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghong","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bihan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyuan","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunhao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baichuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"3515_CR1","doi-asserted-by":"publisher","first-page":"F1843","DOI":"10.1152\/ajprenal.00184.2018","volume":"315","author":"Y Muroya","year":"2018","unstructured":"Muroya, Y. et al. 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