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缺氧预处理的脂肪间充质干细胞外泌体通过激活AKT/HIF-1α轴加速角质形成细胞增殖和迁移来促进阴道伤口愈合。

Hypoxic Preconditioned ADSC Exosomes Enhance Vaginal Wound Healing via Accelerated Keratinocyte Proliferation and Migration Through AKT/HIF‑1α Axis Activation.

作者信息

Yang Xiaoyun, Zhang Shasha, Chen Kewei, Shen Dongsheng, Yang Yang, Shen Aiqun, Liang Junhua, Xu Mengjiao, Yang Yuanyuan, Zhao Yanhong, Li Huaifang, Tong Xiaowen

机构信息

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji University School of Medicine, No. 389 Xincun Road, Shanghai, 200065 People's Republic of China.

Department of Anesthesiology, Tongji Hospital, Tongji University School of Medicine, No. 389 Xincun Road, Shanghai, 200065 People's Republic of China.

出版信息

Cell Mol Bioeng. 2024 Sep 4;17(4):295-303. doi: 10.1007/s12195-024-00814-1. eCollection 2024 Aug.

DOI:10.1007/s12195-024-00814-1
PMID:39372552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11450125/
Abstract

PURPOSE

Accelerating wound healing is a main consideration in surgery. The three stages of wound healing are inflammatory response, tissue repair and cell proliferation. Much research has focused on epidermal cell proliferation and migration because this is an essential step in wound healing.

METHODS AND RESULTS

The current study discovered that exosomes from Adipose-derived stem cell (ADSC) following hypoxic preconditioning (HExo) have a greater promotional effect on vaginal wound healing. Protein kinase B (AKT)/hypoxia-inducible factor 1-alpha (HIF-1α) play an important role in HExo-mediated HaCaT cell migration and proliferation. The promotional effect of HExo on rat wound healing was reversed by both, HIF‑1α and AKT inhibition. Phosphorylation of AKT (p-AKT) or HIF‑1α suppression reversed the protective effect of HExo on vaginal wound healing.

CONCLUSION

Taken together, our study found that hypoxic preconditioning of adipose MSC exosomes enhances vaginal wound healing via accelerated keratinocyte proliferation and migration through AKT/HIF‑1α axis activation.

摘要

目的

加速伤口愈合是外科手术中的一个主要考量因素。伤口愈合的三个阶段为炎症反应、组织修复和细胞增殖。许多研究都聚焦于表皮细胞增殖和迁移,因为这是伤口愈合的关键步骤。

方法与结果

当前研究发现,缺氧预处理后的脂肪干细胞来源外泌体(HExo)对阴道伤口愈合具有更强的促进作用。蛋白激酶B(AKT)/缺氧诱导因子1α(HIF-1α)在HExo介导的HaCaT细胞迁移和增殖中发挥重要作用。HIF-1α和AKT抑制均可逆转HExo对大鼠伤口愈合的促进作用。AKT磷酸化(p-AKT)或HIF-1α抑制可逆转HExo对阴道伤口愈合的保护作用。

结论

综上所述,我们的研究发现,脂肪间充质干细胞外泌体的缺氧预处理通过激活AKT/HIF-1α轴加速角质形成细胞增殖和迁移,从而增强阴道伤口愈合。

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引用本文的文献

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Mesenchymal stem cells from perinatal tissues promote diabetic wound healing via PI3K/AKT activation.围产期组织来源的间充质干细胞通过激活PI3K/AKT促进糖尿病伤口愈合。
Stem Cell Res Ther. 2025 Feb 8;16(1):59. doi: 10.1186/s13287-025-04141-8.

本文引用的文献

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Exosomes from hypoxia-pretreated adipose-derived stem cells attenuate ultraviolet light-induced skin injury via delivery of circ-Ash1l.缺氧预处理脂肪来源干细胞外泌体通过递送circ-Ash1l减轻紫外线诱导的皮肤损伤。
Photodermatol Photoimmunol Photomed. 2023 Mar;39(2):107-115. doi: 10.1111/phpp.12857. Epub 2023 Jan 12.
2
Hypoxia-pretreated ADSC-derived exosome-embedded hydrogels promote angiogenesis and accelerate diabetic wound healing.缺氧预处理的脂肪来源干细胞衍生外泌体包埋水凝胶促进血管生成并加速糖尿病伤口愈合。
Acta Biomater. 2023 Feb;157:175-186. doi: 10.1016/j.actbio.2022.11.057. Epub 2022 Dec 9.
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Exosomes from Adipose Stem Cells Promote Diabetic Wound Healing through the eHSP90/LRP1/AKT Axis.脂肪干细胞来源的外泌体通过 eHSP90/LRP1/AKT 轴促进糖尿病创面愈合。
Cells. 2022 Oct 14;11(20):3229. doi: 10.3390/cells11203229.
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Therapeutic potential of exosomes from adipose-derived stem cells in chronic wound healing.脂肪来源干细胞外泌体在慢性伤口愈合中的治疗潜力
Front Surg. 2022 Sep 30;9:1030288. doi: 10.3389/fsurg.2022.1030288. eCollection 2022.
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Hypoxic ADSC-derived exosomes enhance wound healing in diabetic mice via delivery of circ-Snhg11 and induction of M2-like macrophage polarization.低氧诱导脂肪间充质干细胞来源的外泌体通过递送 circ-Snhg11 并诱导 M2 样巨噬细胞极化增强糖尿病小鼠的伤口愈合。
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