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REVIEW article

Front. Endocrinol.

Sec. Clinical Diabetes

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1603150

This article is part of the Research TopicHighlights in Diabetes NephropathyView all 19 articles

FoxO3a: Capture the Bond Between Magnesium and Diabetic Kidney Disease

Provisionally accepted
Taoran  ChenTaoran ChenMiao  SunMiao SunQi  ZhouQi ZhouJiancheng  XuJiancheng Xu*
  • First Affiliated Hospital of Jilin University, Changchun, China

The final, formatted version of the article will be published soon.

Hyperglycemia in Diabetic Kidney Disease (DKD) induces excessive accumulation of reactive oxygen species (ROS) through various pathways, leading to oxidative stress, ferroptosis, and mitochondrial dysfunction, which collectively contribute to kidney damage.Currently, the treatment of DKD remains a significant challenge. Magnesium, an essential mineral, has emerged as a promising therapeutic agent for DKD due to its anti-inflammatory and antioxidant properties. Magnesium has been shown to alleviate renal fibrosis, maintain tubular integrity and function, improve endothelial cell function, and regulate renal hemodynamics. As a cofactor of antioxidant enzymes, Magnesium directly scavenges ROS and enhances the expression of antioxidant proteins. This review explores the relationship between Magnesium and DKD, examining how Magnesium mitigates oxidative stress through the PI3K/AKT/FoxO3a pathway, inhibits ferroptosis in renal tubular epithelial cells via the AMPK/FoxO3a/Nrf2 pathway, and reduces autophagy and apoptosis, thereby delaying DKD progression. The review further discusses how Magnesium regulates the pivotal FoxO3a protein, a transcription factor with antioxidant properties, leading to the prevention of DKD, andproposes Magnesium supplementation as a potential clinical strategy for alleviating DKD, offering a new therapeutic approach for its treatment.

Keywords: FoxO3a, Magnesium, Oxidative Stress, ferroptosis, Diabetic kidney disease

Received: 31 Mar 2025; Accepted: 26 Jul 2025.

Copyright: © 2025 Chen, Sun, Zhou and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Jiancheng Xu, First Affiliated Hospital of Jilin University, Changchun, China

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