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脂肪间充质干细胞外泌体通过激活 AKT/HIF-1α 轴促进角质形成细胞迁移和增殖,从而加速伤口愈合。

Adipose mesenchymal stem cell exosomes promote wound healing through accelerated keratinocyte migration and proliferation by activating the AKT/HIF-1α axis.

机构信息

Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi, 710032, China.

出版信息

J Mol Histol. 2020 Aug;51(4):375-383. doi: 10.1007/s10735-020-09887-4. Epub 2020 Jun 19.

Abstract

Accelerating wound healing is a key consideration for surgeons. The three stages of wound healing include the inflammatory response, cell proliferation and tissue repair, and much research has focused on the migration and proliferation of epidermal cells, since this is one of the most important steps in wound healing. Studies have shown that adipose mesenchymal stem cells (ADSCs) can promote wound healing by releasing exosomes, although the specific mechanism remains unclear. To clarify the role of adipose mesenchymal stem cell exosomes (ADSCs-exo), we constructed a HaCaT cells model and a mouse wound healing model to examine the effects of ADSCs-exo on wound healing. CCK8 assays and the scratch test showed that ADSCs-exo could promote the proliferation and migration of HaCaT cells. Western blotting and real-time PCR showed that ADSCs-exo upregulated the phosphorylation of AKT and the expression of HIF-1α in HaCaT cells. HIF-1α expression was reduced by inhibiting AKT phosphorylation,and the migration of HaCaT cells simultaneously slowed. These results were also confirmed in vivo. In conclusion, we confirmed that ADSCs-exo promote the proliferation and migration of HaCaT cells by regulating the activation of the AKT/HIF-1α signaling pathway, thus promoting wound healing.

摘要

促进伤口愈合是外科医生的关键考虑因素。伤口愈合的三个阶段包括炎症反应、细胞增殖和组织修复,许多研究都集中在表皮细胞的迁移和增殖上,因为这是伤口愈合最重要的步骤之一。研究表明,脂肪间充质干细胞(ADSCs)可以通过释放外泌体来促进伤口愈合,尽管具体机制尚不清楚。为了阐明脂肪间充质干细胞外泌体(ADSCs-exo)的作用,我们构建了 HaCaT 细胞模型和小鼠伤口愈合模型,以研究 ADSCs-exo 对伤口愈合的影响。CCK8 检测和划痕实验表明 ADSCs-exo 可促进 HaCaT 细胞的增殖和迁移。Western blot 和实时 PCR 结果显示 ADSCs-exo 可上调 HaCaT 细胞中 AKT 的磷酸化和 HIF-1α 的表达。抑制 AKT 磷酸化可降低 HIF-1α 的表达,同时 HaCaT 细胞的迁移也会减缓。这些结果在体内也得到了验证。综上所述,我们证实 ADSCs-exo 通过调节 AKT/HIF-1α 信号通路的激活促进 HaCaT 细胞的增殖和迁移,从而促进伤口愈合。

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