Adipose mesenchymal stem cell-derived exosomes promote skin wound healing in diabetic mice by regulating epidermal autophagy
- Burns & Trauma Vol. 12, Issue 1, (2024)
- 作者机构：
1. Department of Pathology, Shengjing Hospital of China Medical University
2. Department of Pathology
3. Huazhong University of Science and Technology
4. Medical Research Center, Shengjing Hospital of China Medical University
5. Department of Stem Cells and Regenerative Medicine
6. China Medical University
7. Department of General Surgery, Shengjing Hospital of China Medical University
- 作者简介：
- 基金信息：
DOI：10.1093/burnst/tkae001
CLC：Published：2024，
Published Online：29 February 2024，
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Haiyue Ren, Peng Su, Feng Zhao, Qiqi Zhang, Xing Huang, Cai He, Quan Wu, Zitong Wang, Jiajie Ma, Zhe Wang, Adipose mesenchymal stem cell-derived exosomes promote skin wound healing in diabetic mice by regulating epidermal autophagy, Burns & Trauma, Volume 12, 2024, tkae001, https://doi.org/10.1093/burnst/tkae001
Haiyue Ren, Peng Su, Feng Zhao, Qiqi Zhang, Xing Huang, Cai He, Quan Wu, Zitong Wang, Jiajie Ma, Zhe Wang, Adipose mesenchymal stem cell-derived exosomes promote skin wound healing in diabetic mice by regulating epidermal autophagy, Burns & Trauma, Volume 12, 2024, tkae001, https://doi.org/10.1093/burnst/tkae001 DOI：
摘要
Abstract
BackgroundAdipose mesenchymal stem cell-derived exosomes (ADSC-Exos) have great potential in the field of tissue repair and regenerative medicine
particularly in cases of refractory diabetic wounds. Interestingly
autophagy plays a role in wound healing
and recent research has demonstrated that exosomes are closely associated with intracellular autophagy in biogenesis and molecular signaling mechanisms. Therefore
this study aimed to investigate whether ADSC-Exos promote the repair of diabetic wounds by regulating autophagy to provide a new method and theoretical basis for the treatment of diabetic wounds.MethodsWestern blot analysis and autophagy double-labelled adenovirus were used to monitor changes in autophagy flow in human immortalized keratinocyte cell line (HaCaT) cells. ADSC-Exos were generated from ADSC supernatants via ultracentrifugation. The effectiveness of ADSC-Exos on HaCaT cells was assessed using a live-cell imaging system
cell counting kit-8 and cell scratch assays. The cells were treated with the autophagy inhibitor bafilomycin A1 to evaluate the effects of autophagy on cell function. The recovery of diabetic wounds after ADSC-Exo treatment was determined by calculating the healing rates and performing histological analysis. High-throughput transcriptome sequencing was used to analyze changes in mRNA expression after the treatment of HaCaT cells with ADSC-Exos.ResultsADSC-Exos activated autophagy in HaCaT cells
which was inhibited by high glucose levels
and potentiated their cellular functions. Moreover
ADSC-Exos in combination with the autophagy inhibitor bafilomycin A1 showed that autophagy defects further impaired the biological function of epidermal cells under high-glucose conditions and partially weakened the healing effect of ADSC-Exos. Using a diabetes wound model
we found that ADSC-Exos promoted skin wound healing in diabetic mice
as evidenced by increased epidermal autophagy and rapid re-epithelialization. Finally
sequencing results showed that increased expression of autophagy-related genes nicotinamide phosphoribosyltransferase (NAMPT)
CD46
vesicle-associated membrane protein 7 (VAMP7)
VAMP3 and eukaryotic translation initiation factor 2 subunit alpha (EIF2S1) may contribute to the underlying mechanism of ADSC-Exo action.ConclusionsThis study elucidated the molecular mechanism through which ADCS-Exos regulate autophagy in skin epithelial cells
thereby providing a new theoretical basis for the treatment and repair of skin epithelial damage by ADSC-Exos.
关键词
Keywords
Adipose-derived mesenchymal stem cellsExosomesAutophagydiabetesSkin wound healingEpidermal cellsTissue repairRegeneration
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