Hyperbaric oxygen potentiates diabetic wound healing by promoting fibroblast cell proliferation and endothelial cell angiogenesis

Huang, Xu; Liang, Pengfei; Jiang, Bimei; Zhang, Pihong; Yu, Wenchang; Duan, Mengting; Guo, Le; Cui, Xu; Huang, Mitao; Huang, Xiaoyuan

doi:10.1016/j.lfs.2020.118246

Cited by 109 publications

(80 citation statements)

References 46 publications

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“…Interactions between fibroblasts and endothelial cells are crucial for angiogenesis (20,21). The failure of diabetic wounds to heal efficiently is due to reduced vascular endothelial cell proliferation and epithelial cell migration coupled with severe inflammatory conditions in the epidermis (22). Expression of PCNA, a protein involved in DNA replication, is upregulated during the late G1 phase and S phase of the cell cycle, and is thus considered a useful nuclear marker of proliferation (23).…”

Section: Discussionmentioning

confidence: 99%

Diabetic ferroptosis plays an important role in triggering on inflammation in diabetic wound

et al. 2021

American Journal of Physiology-Endocrinology and Metabolism

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Impaired wound healing is a major complication of diabetes and involves sustained inflammation and oxidative stress at the wound site. Here, we investigated the potential involvement of ferroptosis, a newly discovered form of cell death characterized by iron-dependent accumulation of lipid peroxides, in the pathogenesis of diabetic wound healing. Fibroblasts and vascular endothelial cells exposed to high glucose concentrations in vitro contained elevated levels of reactive oxygen species (ROS), lipid peroxidation products, and ferroptosis-associated proteins, and displayed reduced survival and migration. These effects of high glucose were all significantly reduced by treatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1). Similarly, in a rat model of diabetes, direct application of Fer-1 to the wound site reduced the expression of oxidative stress and inflammation markers and accelerated wound healing via activation of the anti-inflammatory phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. Our results implicate ferroptosis in wound healing and identify a potential new therapeutic target for difficult-to-treat diabetic wounds.

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Section: Discussionmentioning

confidence: 99%

Diabetic ferroptosis plays an important role in triggering on inflammation in diabetic wound

et al. 2021

American Journal of Physiology-Endocrinology and Metabolism

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“…Endothelial cell is one of the most important functional cells in skin and plays a critical role in wound healing by participating in angiogenesis ( 8 , 36 ). We therefore tested the effect of IL-25 on HUVECs under high glucose (HG) conditions by adding recombinant human IL-25 protein (rhIL-25).…”

Section: Resultsmentioning

confidence: 99%

Interleukin-25-Mediated-IL-17RB Upregulation Promotes Cutaneous Wound Healing in Diabetic Mice by Improving Endothelial Cell Functions

et al. 2022

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Diabetic foot ulcer (DFU) frequently leads to non-traumatic amputation and finally even death. However, the mechanism of DFU is not fully understood. Interleukin 25 (IL-25), an alarmin cytokine that responds to tissue injury, has been reported to participate in tissue regeneration and maintaining glucose homeostasis. However, the role of IL-25 in diabetic wound healing remains unknown. Here, we showed that interleukin 17 receptor B (IL-17RB), the functional receptor of IL-25, was significantly inhibited in the wound skin of both diabetic patients with DFU and streptozotocin (STZ)-induced diabetic mice. Topical administration of recombinant IL-25 protein improved angiogenesis and collagen deposition in the wound bed and thus ameliorated delayed diabetic wound healing. IL-25 increased endothelial-specific CD31 expression in diabetic wounds and exogenous IL-25 protected endothelial cells from high glucose-impaired cell migration and tube formation in vitro. We further revealed that IL-25-mediated-IL-17RB signaling rescued the downregulation of Wnt/β-catenin pathway both in vivo in diabetic mice and in vitro in HUVECs and induced the phosphorylation of AKT and ERK 1/2 in HUVECs under high glucose conditions. This study defines a positive regulatory role of IL-25-mediated-IL-17RB signaling in diabetic wound healing and suggests that induction of IL-25-mediated-IL-17RB signaling may be a novel therapeutic strategy for treating poor healing diabetic wounds.

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“…PA classification could allow wound specialists to change their course of treatment if the wound is not responding to conventional treatment protocols. (15,25,53,54) This would in turn improve outcomes, reduce amputations, healing time, and costs.…”

Section: Clinical Significancementioning

confidence: 99%

Photoacoustic monitoring of angiogenesis predicts response to therapy in healing wounds

Mantri

Tsujimoto

Donovan

et al. 2021

Preprint

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Chronic wounds are a major health problem that cause the medical infrastructure billions of dollars every year. Chronic wounds are often difficult to heal and cause significant discomfort. Although wound specialists have numerous therapeutic modalities at their disposal, tools that could 3D-map wound bed physiology and guide therapy do not exist. Visual cues are the current standard but are limited to surface assessment; clinicians rely on experience to predict response to therapy. Photoacoustic (PA) ultrasound (US) is a non-invasive, hybrid imaging modality that can solve these major limitations. PA relies on the contrast generated by hemoglobin in blood which allows it to map local angiogenesis, tissue perfusion and oxygen saturation - all critical parameters for wound healing. This work evaluates the use of PA-US to monitor angiogenesis and stratify patients responding vs. not-responding to therapy. We imaged 19 patients with 22 wounds once a week for at least three weeks. Our findings suggest that PA imaging directly visualizes angiogenesis. Patients responding to therapy showed clear signs of angiogenesis and an increased rate of PA increase (p = 0.002). These responders had a significant and negative correlation between PA intensity and wound size. Hypertension was correlated to impaired angiogenesis in non-responsive patients. The rate of PA increase and hence the rate of angiogenesis was able to predict healing times within 30 days from the start of monitoring (power = 88%, alpha = 0.05) This early response detection system could help inform management and treatment strategies while improving outcomes and reducing costs.

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Hyperbaric oxygen potentiates diabetic wound healing by promoting fibroblast cell proliferation and endothelial cell angiogenesis

Cited by 109 publications

References 46 publications

Diabetic ferroptosis plays an important role in triggering on inflammation in diabetic wound

Diabetic ferroptosis plays an important role in triggering on inflammation in diabetic wound

Interleukin-25-Mediated-IL-17RB Upregulation Promotes Cutaneous Wound Healing in Diabetic Mice by Improving Endothelial Cell Functions

Photoacoustic monitoring of angiogenesis predicts response to therapy in healing wounds

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