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

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

  • J Invest Dermatol. 2023 Oct 12:S0022-202X(23)02951-2. doi: 10.1016/j.jid.2023.08.030.
Hailin Xu 1 Hao Yang 1 Zhiyong Wang 1 Qizhi Tang 2 Xiaoling Cao 1 Chufen Chen 1 Yunxian Dong 1 Zhongye Xu 1 Dongming Lv 1 Yanchao Rong 1 Miao Chen 2 Bing Tang 1 Wuguo Deng 3 Jiayuan Zhu 4 Zhicheng Hu 4
Affiliations

Affiliations

  • 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. Electronic address: huzhch5@mail.sysu.edu.cn.
  • 4 First Affiliated Hospital of Sun Yat-sen University, Burn department, Guangzhou 51080, China. Electronic address: huzhch5@mail.sysu.edu.cn.
Abstract

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.

Keywords

apoptosis; diabetes; diabetic wound; endothelial cell; exosomes; stem cell.

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Products
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  • HY-15534
    99.0%, Mitochondrial Membrane Potential Probe