Background

Adipose mesenchymal stem cell (AMSC)-derived exosomes are promising novel factors for wound repair and regeneration. This study aimed to explore the potential roles and underlying mechanisms of specific miRNA in wound healing using AMSC-derived exosomes as carriers.

Methods

The expression profiles of GSE197840 were downloaded to screen for differentially expressed miRNAs (DEmiRNAs), and the corresponding genes of the identified miRNAs were predicted. Next, miRNA-mRNA co-expression networks were constructed and the genes in these networks were subjected to functional analysis. miR-223–3p overexpressed AMSCs were then established to isolate exosomes, and the effects of AMSC-derived exosomes carrying miR-223–3p on wound healing and the related potential mechanisms were further investigated in vivo.

Results

35 DEmiRNAs were identified and a co-expression network containing 22 miRNAs and 91 target genes was constructed. Based on the network, miR-223–3p was the hub node and the genes were significantly enriched in 15 GO terms of biological processes and 14 KEGG pathways, including cAMP, PI3K-Akt, cGMP-PKG, neurotrophin signaling pathway, and dopaminergic synapse. Then, miR-223–3p overexpressed AMSCs-derived exosomes were successfully extracted, and miR-223–3p was found to directly bind with MAPK10. In vivo experiments validated that AMSCs-derived exosomal miR-223–3p could promote wound healing, and up-regulated α-SMA, CD31, COL1A1, COL2A1, COL3A1, and down-regulated MAPK10, TNF-α, IL-β, and IL-6.

Conclusions

AMSC-derived exosomal miR-223–3p may accelerate wound healing by targeting MAPK10.

中文翻译：

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MiR-223–3p 过表达脂肪间充质干细胞来源的外泌体通过靶向 MAPK10 促进伤口愈合

背景

脂肪间充质干细胞（AMSC）衍生的外泌体是有希望的伤口修复和再生的新因子。本研究旨在以AMSC衍生的外泌体为载体，探讨特定miRNA在伤口愈合中的潜在作用和潜在机制。

方法

下载GSE197840的表达谱来筛选差异表达的miRNA（DEmiRNA），并预测鉴定出的miRNA的相应基因。接下来，构建miRNA-mRNA共表达网络并对这些网络中的基因进行功能分析。然后建立miR-223–3p过表达的AMSC来分离外泌体，并在体内进一步研究携带miR-223–3p的AMSC衍生的外泌体对伤口愈合的影响以及相关的潜在机制。

结果

鉴定出 35 个 DEmiRNA，并构建了包含 22 个 miRNA 和 91 个靶基因的共表达网络。基于网络，miR-223–3p为枢纽节点，基因显着富集于生物过程的15个GO项和14个KEGG通路，包括cAMP、PI3K-Akt、cGMP-PKG、神经营养素信号通路和多巴胺能突触。然后，成功提取了过表达miR-223–3p的AMSCs来源的外泌体，并发现miR-223–3p直接与MAPK10结合。体内实验证实，AMSCs 来源的外泌体 miR-223–3p 可以促进伤口愈合，上调 α-SMA、 CD31、COL1A1、COL2A1、COL3A1，下调 MAPK10、TNF-α、IL-β和白细胞介素-6。

结论

AMSC 衍生的外泌体 miR-223-3p 可能通过靶向 MAPK10 加速伤口愈合。