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Review | Open Access

Elucidating the dual roles of apoptosis and necroptosis in diabetic wound healing: implications for therapeutic intervention

Xingqian Wu1,2 , Rifang Gu3, Ming Tang4, Xingrui Mu1,2, Wenjie He1,2, Xuqiang Nie1,2 ( )
College of Pharmacy, Zunyi Medical University, No. 6 West Xuefu Road, Xinpu New District, Zunyi 563006, China
Key Lab of the Basic Pharmacology of the Ministry of Education & Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, No. 6 West Xuefu Road, Xinpu New District, Zunyi 563006, China
School Medical Office, Zunyi Medical University, No. 6 West Xuefu Road, Xinpu New District, Zunyi 563006, China
Department of Structural Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, United States
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Highlights

• Dual regulation of apoptosis and necroptosis is crucial for optimal diabetic wound healing.

• Hyperglycemia-induced oxidative stress alters the balance between apoptosis and necroptosis in diabetic wounds.

• MicroRNAs emerge as potential biomarkers and therapeutic targets in modulating cell death pathways during wound healing.

• Targeting the RIPK3 pathway shows promise in reducing inflammation and promoting wound repair in diabetic conditions.

• Combination therapies addressing multiple cell death pathways may offer synergistic benefits in treating diabetic wounds.

Abstract

Wound healing is a complex and multistep biological process that involves the cooperation of various cell types. Programmed cell death, including apoptosis and necrotizing apoptosis, plays a crucial role in this process. Apoptosis, a controlled and orderly programmed cell death regulated by genes, helps eliminate unnecessary or abnormal cells and maintain internal environmental stability. It also regulates various cell functions and contributes to the development of many diseases. In wound healing, programmed cell death is essential for removing inflammatory cells and forming scars. On the other hand, necroptosis, another form of programmed cell death, has not been thoroughly investigated regarding its role in wound healing. This review explores the changes and apoptosis of specific cell groups during wound healing after an injury and delves into the potential underlying mechanisms. Furthermore, it briefly discusses the possible mechanisms linking wound inflammation and fibrosis to apoptosis in wound healing. By understanding the relationship between apoptosis and wound healing and investigating the molecular mechanisms involved in apoptosis regulation, new strategies for the clinical treatment of wound healing may be discovered.

References

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Burns & Trauma
Article number: tkae061

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Cite this article:
Wu X, Gu R, Tang M, et al. Elucidating the dual roles of apoptosis and necroptosis in diabetic wound healing: implications for therapeutic intervention. Burns & Trauma, 2025, 13(2): tkae061. https://doi.org/10.1093/burnst/tkae061

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Received: 08 May 2024
Revised: 27 August 2024
Accepted: 28 August 2024
Published: 10 October 2026
© The Author(s) 2024. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com