ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1558443
Hydrogen sulfide as a therapeutic agent for diabetic wounds: effects on inflammation and fibroblast pyroptosis
Provisionally accepted
Fusheng Zhao
Yuanyuan Li
Qunying HuJiali XuNa ZhangYonglan ChenXinyue JiangChunfu GuKexin Zhang
Geng Wu*- Mudanjiang Medical University, Mudanjiang, China
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Introduction: Chronic nonhealing wounds are one of the most serious complications of diabetes mellitus (DM), with limited treatment options. Hydrogen sulfide (H 2 S) plays a protective role against multiple inflammatory diseases. This study aimed to explore the effects of H 2 S on diabetic skin wound healing and its underlying mechanisms.Methods: A streptozotocin-induced diabetic rat model was established, and the rats were randomly divided into control, DM, and DM + NaHS (a donor of H 2 S) groups. Full-thickness wounds were made on the dorsal skin of the rats. H 2 S levels and H 2 S-synthesizing enzyme expression were evaluated in the wound tissue. Wound healing, histological changes, inflammasome activation, fibroblast pyroptosis, and phosphorylation of signaling components of nuclear factor kappa B (NF-κB) pathway were assessed.Results: The results showed that NaHS administration effectively restored H 2 S levels and promoted skin wound healing, as evidenced by the amelioration of histological changes and increased collagen deposition in diabetic rats. Meanwhile, NaHS treatment inhibited macrophage M1 polarization and decreased the levels of pro-inflammatory cytokines, such as tumor necrosis factor- (TNF-α), interleukin-1 (IL-1β), and interleukin-6 (IL-6) in diabetic wound tissues, notably, suppressing NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and fibroblast pyroptosis. In addition, NaHS treatment was able to inhibit the activation of NF-κB pathway in the wound tissues.Discussion: Taken together, these results show that H 2 S promotes skin wound healing in diabetic rats and may be involved in the restoration of H 2 S levels, inhibition of NLRP3 inflammasome activation, and fibroblast pyroptosis, suggesting that it may be a promising therapeutic agent for treating diabetic skin wounds.
Keywords: Hydrogen Sulfide, diabetic skin wound healing, Skin fibroblast, NLRP3 inflammasome, pyroptosis, PI3K/Akt/mTOR pathway
Received: 10 Jan 2025; Accepted: 28 Jul 2025.
Copyright: © 2025 Zhao, Li, Hu, Xu, Zhang, Chen, Jiang, Gu, Zhang and Wu. 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: Geng Wu, Mudanjiang Medical University, Mudanjiang, China
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