Sun HJ, Si SW, Ma YM, Liu XK, Geng HF, Liang J. Role of nuclear factor erythroid 2-related factor 2 in negative pressure wound therapy for diabetic foot ulcers. World J Diabetes 2025; 16(5): 104350 [DOI: 10.4239/wjd.v16.i5.104350]
Corresponding Author of This Article
Jun Liang, PhD, Professor, Department of Endocrinology, Xuzhou Central Hospital, No. 199 Jiefang South Road, Xuzhou 221009, Jiangsu Province, China. mwlj521@njmu.edu.cn
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Hao-Jie Sun, Xue-Kui Liu, Hou-Fa Geng, Jun Liang, Department of Endocrinology, Xuzhou Central Hospital, Xuzhou 221009, Jiangsu Province, China
Shan-Wen Si, Department of Scientific Research, Fuyang Hospital of Anhui Medical University, Fuyang 236112, Anhui Province, China
Ya-Mei Ma, Electrocardiogram Room, Fuyang Hospital of Anhui Medical University, Fuyang 236112, Anhui Province, China
Co-first authors: Hao-Jie Sun and Shan-Wen Si.
Co-corresponding authors: Hou-Fa Geng and Jun Liang.
Author contributions: Sun HJ, Geng HF, and Liang J contributed to the conception and design of the study; Si SW and Ma YM contributed to the data collection and assembly; Si SW contributed to the sample experiment; Liu XK contributed to the data analysis and interpretation; Sun HJ, Si SW, and Ma YM contributed to manuscript writing; All authors have read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by Ethics Committee of Xuzhou Central Hospital (No. XZXY-LK-20211223-053).
Institutional animal care and use committee statement: This study does not involve animals.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: The data used in the current study are available from the corresponding author on reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jun Liang, PhD, Professor, Department of Endocrinology, Xuzhou Central Hospital, No. 199 Jiefang South Road, Xuzhou 221009, Jiangsu Province, China. mwlj521@njmu.edu.cn
Received: December 18, 2024 Revised: January 27, 2025 Accepted: March 3, 2025 Published online: May 15, 2025 Processing time: 128 Days and 16.4 Hours
Abstract
BACKGROUND
Negative pressure wound therapy (NPWT) is a potential treatment for diabetic foot ulcers (DFUs), although the mechanisms underlying its effectiveness remain unclear. This study posits that NPWT may improve wound healing by promoting angiogenesis and activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like epichlorohydrin-associated protein 1 (Keap1) signaling pathway, which is crucial for the body’s defense against oxidative stress. The hypothesis indicates that enhancing antioxidant defenses through NPWT may positively affect the healing process. There are still limited data on the roles of Nrf2, its downstream signaling molecules, and angiogenesis markers in patients undergoing NPWT.
AIM
To study the mechanism of NPWT in DFUs.
METHODS
This study included a total of 40 hospitalized patients with DFUs from Xuzhou Central Hospital, who were divided into Control group (n = 21) and NPWT group (n = 19). The levels of Nrf2 and Keap1 were analyzed in the granulation tissue 7 days after treatment. The wound condition, erythrocyte sedimentation rate (ESR), procalcitonin (PCT), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), cluster of differentiation 31 (CD31), and levels of oxidative stress [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC)] were analyzed before and 7 days after treatment by the Mann-Whitney U test.
RESULTS
The NPWT group demonstrated significant improvements in wound healing compared to the control group after 7 days of treatment. The levels of ESR, PCT, IL-6, and TNF-α were significantly reduced in the NPWT group compared to the control group (P < 0.05), while the levels of CD31, VEGF, and b-FGF showed significant increases (P < 0.05). The NPWT group exhibited notable elevations in the levels of Nrf2 and its downstream targets (SOD, CAT, and T-AOC), accompanied by decreases in the levels of Keap1 and MDA (P < 0.05).
CONCLUSION
NPWT may contribute to the healing of DFUs by potentially reducing levels of oxidative stress. Its effects could possibly be enhanced through the action of Nrf2.
Core Tip: This study investigated the potential of negative pressure wound therapy (NPWT) in diabetic foot ulcers (DFUs) by assessing wound healing, inflammatory markers, cytokines, growth factors, and oxidative stress. NPWT was associated with improved wound conditions and reduced inflammation, while also increasing angiogenesis markers and antioxidant defenses that may be mediated by nuclear factor erythroid 2-related factor 2 (Nrf2). The study suggests that Nrf2 could be involved in the therapeutic effects of NPWT on DFUs.
