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Erratum
- Erratum: Figure Correction
- 4-Octyl Itaconate Promotes Diabetic Wound Healing by Enhancing Pro-Resolving Macrophages via the Efferocytosis-MCT1-Lactate-GPR132 Pathway and Macrophage-Independent Synergistic Effects
- Mengqin Tu, Xiaoli Zou, Xiaozhen Tan, Yijun Liu, Xinxu Ge, Yu Hu, Qiuyue Peng, Linlin Huang, Yan Zeng, Chunxia Jia, Man Guo, Jiao Chen, Yang Long, Yong Xu
- Published online August 5, 2026
- DOI: https://doi.org/10.4093/dmj.2024.0579.e1 [Epub ahead of print]
- Corrects: Diabetes Metab J 2026;50(4):707
- 297 View
- 9 Download
Original Article
- Basic and Translational Research
- 4-Octyl Itaconate Promotes Diabetic Wound Healing by Enhancing Pro-Resolving Macrophages via the Efferocytosis-MCT1-Lactate-GPR132 Pathway and Macrophage-Independent Synergistic Effects
- Mengqin Tu, Xiaoli Zou, Xiaozhen Tan, Yijun Liu, Xinxu Ge, Yu Hu, Qiuyue Peng, Linlin Huang, Yan Zeng, Chunxia Jia, Man Guo, Jiao Chen, Yang Long, Yong Xu
- Diabetes Metab J. 2026;50(4):707-723. Published online November 3, 2025
- DOI: https://doi.org/10.4093/dmj.2024.0579
- Correction in: https://doi.org/
- 6,547 View
- 181 Download
- 3 Web of Science
- 4 Crossref
-
Abstract
PDF
Supplementary Material
PubReader 
ePub - Background
Diabetic foot ulcers are a severe diabetic complication characterized by poor healing. Itaconate, a tricarboxylic acid cycle byproduct, has been shown to improve wound healing. This study investigated the potential of 4-octyl itaconate (4-OI), an esterified derivative of itaconate, to modulate efferocytosis and macrophage pro-resolving function to promote diabetic wound healing.
Methods
A diabetic mouse wound model was used. For in vitro analysis, RAW264.7 macrophages and apoptotic Jurkat cells were cocultured under high glucose conditions (HG, 30 mM). To further evaluate the roles of macrophages, monocarboxylate transporter 1 (MCT1), and lactate in 4-OI-promoted diabetic wound healing, we used clodronate-liposomes (CLD-Lipo) to deplete macrophages, AZD3965 as an MCT1 inhibitor, and telmisartan to validate our hypothesis.
Results
In diabetic mice, impaired clearance of apoptotic neutrophils and persistent M1 activation delayed wound healing. 4-OI improved diabetic wound repair by enhancing efferocytosis, shifting macrophages toward an M2 pro-resolving phenotype, and boosting angiogenesis. 4-OI showed a protective effect mediated by macrophages, while endothelial cells and neutrophils also played synergistic roles in diabetic wound healing. Moreover, 4-OI upregulated MCT1, which, in turn, increased the release of lactate triggered by efferocytosis at the wound site. Lastly, we confirmed that the pro-resolving effects of 4-OI onmacrophage function were mediated by promoting pro-resolving macrophage proliferation and polarization via efferocytosis-induced lactate release and subsequent activation of G protein-coupled receptor 132 (GPR132).
Conclusion
4-OI promotes diabetic wound healing through macrophage-dependent and macrophage-independent mechanisms. Moreover, the protective effect of 4-OI on macrophages was mediated through MCT1-mediated lactate release triggered by efferocytosis and subsequent GPR 132 activation. -
Citations
Citations to this article as recorded by
- Roles of efferocytosis in wound repair: Process, cells, and signals
Yilin Sun, Haiying Guo, Yang Bai, Jin Chen, Yuhong Li
Genes & Diseases.2026; 13(3): 101937. CrossRef - 4-Octyl Itaconate Promotes Diabetic Wound Healing by Enhancing Pro-Resolving Macrophages via the Efferocytosis-MCT1-Lactate-GPR132 Pathway and Macrophage-Independent Synergistic Effects (Diabetes Metab J 2026;50:707-23)
Muhammad Junaid, Yabin Zhu
Diabetes & Metabolism Journal.2026; 50(4): 818. CrossRef - Efferocytosis: unifying pathogenic hub in metabolic disorders—mechanistic landscapes, targeted therapies and translational bottlenecks
Dongze Li, Yao Huang, Xuanqin Chen, Li Zhang, Qiming Gong, Qifu Li, Yu Li, Yong Xu, Wei Huang
Frontiers in Immunology.2026;[Epub] CrossRef - Diosgenin presents a novel role in promoting diabetic wound healing: A mechanism involving Sirt6/Nrf2-mediated inhibition of ferroptosis
Ji-qi Wang, Lu Chen, Yu-zhe Lin, Xiu-zhi Zhang, Yi-tian Yu, Yi-han Lin, Li-jiang Han, Yi-yun Lv, Nai-feng Tian, Zhen Lin, Wei-jun Guo
Journal of Pharmaceutical Analysis.2026; 16(8): 101635. CrossRef
- Roles of efferocytosis in wound repair: Process, cells, and signals
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