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Epidermal stem cell derived exosomes alleviate excessive autophagy induced endothelial cell apoptosis by delivering miR200b-3p to diabetic wounds

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机构： [1]First Affiliated Hospital of Sun Yat-sen University, Burn department, Guangzhou 51080, China. [2]Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine.Affiliated Nanhai Hospital of Traditional Chinese Medicine of Jinan University, Foshan 528200, China. [3]Sun Yat-sen University Cancer Center.State Key Laboratory of Oncology in South China.Collaborative Innovation Center of Cancer Medicine, Guangzhou 510080, China.

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The dysfunction of endothelial cells caused by hyperglycaemia is observed as a decrease in neovascularization in diabetic wound healing. Studies have found that epidermal stem cells (EpiSCs) can promote the angiogenesis of full-thickness wounds. To further explain the therapeutic effect of EpiSCs, epidermal stem cell-derived exosomes (EpiSC-EXOs) are considered the main substance contributing to stem cell effectivity. In our study, EpiSCs and EpiSC-EXOs were supplied to the dorsal wounds of db/db mouse. Results showed that EpiSCs could colonize in the wound area and both EpiSCs and EpiSC-EXOs could accelerate diabetic wound healing by promoting angiogenesis. In vitro, persistent high glucose led to the malfunction and apoptosis of endothelial cells. The apoptosis induced by high glucose is due to excessive autophagy and was alleviated by EpiSC-EXOs. RNA sequencing of EpiSC-EXOs showed miR200b-3p was enriched in EpiSC-EXOs and alleviated the apoptosis of endothelial cells. Synapse Defective Rho GTPase Homolog 1 (SYDE1) was identified the target of miR200b-3p and affected the phosphorylation of ERK to regulate intracellular autophagy and apoptosis. Furthermore, animal experiments validated the angiogenic effect of miR200b-3p. Collectively, our results verified the effect of EpiSC-EXOs on apoptosis caused by hyperglycaemia in endothelial cells through the miR200b-3p/SYDE1/RAS/ERK/autophagy pathway, providing a theoretical basis for EpiSC in treating diabetic wounds.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

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出版当年[2022]版：

大类 | 1 区

医学

小类 | 1 区皮肤病学

最新[2025]版：

大类 | 2 区医学

小类 | 2 区皮肤病学

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第一作者机构： [1]First Affiliated Hospital of Sun Yat-sen University, Burn department, Guangzhou 51080, China.

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通讯机构： [1]First Affiliated Hospital of Sun Yat-sen University, Burn department, Guangzhou 51080, China. [3]Sun Yat-sen University Cancer Center.State Key Laboratory of Oncology in South China.Collaborative Innovation Center of Cancer Medicine, Guangzhou 510080, China. [*1]First Affiliated Hospital of Sun Yat-sen University, Burn department, Guangzhou, China [*2]State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. [*3]The First Affiliated Hospital of Sun Yat-sen University, Burn department, Guangzhou 510080, China

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Epidermal stem cell derived exosomes alleviate excessive autophagy induced endothelial cell apoptosis by delivering miR200b-3p to diabetic wounds