Application of Deferoxamine in Tissue Regeneration Attributed to Promoted Angiogenesis

Shen, Haijun; Ma, Yane; Qiao, Yi; Zhang, Chun; Chen, Jialing; Zhang, Ran

doi:10.3390/molecules29092050

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2024

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Cited by 4 publications

References 181 publications

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Advancements in diabetic foot ulcer research: Focus on mesenchymal stem cells and their exosomes

Wu,

Zhou,

et al. 2024

Heliyon

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Advancements in diabetic foot ulcer research: Focus on mesenchymal stem cells and their exosomes

Wu,

Zhou,

et al. 2024

Heliyon

View full text Add to dashboard Cite

Advances in nucleic acid delivery strategies for diabetic wound therapy

Sarthi,

Bhardwaj,

Kumar Jangde

2024

Journal of Clinical & Translational Endocrinology

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4-aminopyridine attenuates inflammation and apoptosis and increases angiogenesis to promote skin regeneration following a burn injury in mice

V. G.,

Ellur,

A. Gaber

et al. 2024

Cell Death Discov.

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Severe thermal skin burns are complicated by inflammation and apoptosis, which delays wound healing and contributes to significant morbidity. Diverse treatments demonstrate limited success in mitigating these processes to accelerate healing. Agents that alter cell behavior to improve healing would alter treatment paradigms. We repurposed 4-aminopyridine (4-AP), a drug approved by the US FDA for multiple sclerosis, to treat severe burns in mice (10-week-old C57BL/6 J male mice weighing 25 ± 3 g). We found that 4-AP, in the early stages of burn healing, significantly reduced the expression of pro-inflammatory cytokines IL1β and TNFα while increasing the expression of anti-inflammatory markers CD206, ARG-1, and IL10. We demonstrated increased intracellular calcium effects of 4-AP through Orai1-pSTAT6 signaling, where 4-AP significantly mitigated inflammatory effects by promoting M2 macrophage differentiation in in-vitro macrophages and post-skin burn tissues. 4-AP attenuated apoptosis, with decreases in apoptotic markers BAX, caspase-9, and caspase-3 and increases in anti-apoptotic markers BCL2 and BCL-XL. Furthermore, 4-AP promoted angiogenesis through increases in the expression of CD31, VEGF, and eNOS. Together, these likely contributed to accelerated burn wound closure, as demonstrated in increased keratinocyte proliferation (K14) and differentiation (K10) markers. In the later stages of burn healing, 4-AP increased TGFβ and FGF levels, which are known to mark the transformation of fibroblasts to myofibroblasts. This was further demonstrated by an increased expression of α-SMA and vimentin, as well as higher levels of collagen I and III, MMP 3, and 9 in mice treated with 4-AP. Our findings support the idea that 4-AP may have a novel, clinically relevant therapeutic use in promoting burn wound healing.

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Application of Deferoxamine in Tissue Regeneration Attributed to Promoted Angiogenesis

Cited by 4 publications

References 181 publications

Advancements in diabetic foot ulcer research: Focus on mesenchymal stem cells and their exosomes

Advancements in diabetic foot ulcer research: Focus on mesenchymal stem cells and their exosomes

Advances in nucleic acid delivery strategies for diabetic wound therapy

4-aminopyridine attenuates inflammation and apoptosis and increases angiogenesis to promote skin regeneration following a burn injury in mice

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