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

IF 2.3 4区医学 Q3 BIOPHYSICS Cellular and molecular bioengineering Pub Date : 2024-09-04 DOI:10.1007/s12195-024-00814-1

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

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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.

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缺氧预处理 ADSC 外泌体通过激活 AKT/HIF-1α 轴加速角质形成细胞增殖和迁移促进阴道伤口愈合

目的加速伤口愈合是外科手术的主要考虑因素。伤口愈合的三个阶段是炎症反应、组织修复和细胞增殖。目前的研究发现，缺氧预处理（HExo）后的脂肪来源干细胞（ADSC）外泌体对阴道伤口愈合有更大的促进作用。蛋白激酶B（AKT）/缺氧诱导因子1-α（HIF-1α）在HExo介导的HaCaT细胞迁移和增殖中发挥重要作用。抑制 HIF-1α 和 AKT 可逆转 HExo 对大鼠伤口愈合的促进作用。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可通过激活 AKT/HIF-1α 轴加速角质形成细胞的增殖和迁移，从而促进阴道伤口愈合。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.