Department of Dermatology, The Second Hospital of Dalian Medical University, Dalian 116023, China.
Department of Dermatology, Taizhou Hospital of Zhejiang Province, Taizhou 317000, China.
Acta Histochem. 2023 Dec;125(8):152102. doi: 10.1016/j.acthis.2023.152102. Epub 2023 Oct 12.
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.
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.
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.
AMSC-derived exosomal miR-223-3p may accelerate wound healing by targeting MAPK10.
脂肪间充质干细胞（AMSC）衍生的外泌体是促进伤口修复和再生的有前途的新型因子。本研究旨在探索以 AMSC 衍生的外泌体为载体，特定 miRNA 在伤口愈合中的潜在作用和潜在机制。
下载 GSE197840 表达谱，筛选差异表达 miRNA（DEmiRNA），预测鉴定 miRNA 的相应基因。构建 miRNA-mRNA 共表达网络，并对网络中的基因进行功能分析。构建 miR-223-3p 过表达 AMSC 以分离外泌体，进一步研究 AMSC 衍生的携带 miR-223-3p 的外泌体对伤口愈合的影响及相关潜在机制。
鉴定出 35 个 DEmiRNA，构建了包含 22 个 miRNA 和 91 个靶基因的共表达网络。基于该网络，miR-223-3p 是枢纽节点，基因显著富集于生物过程的 15 个 GO 术语和 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 miR-223-3p 过表达 AMSC 衍生的外泌体，并发现 miR-223-3p 可直接与 MAPK10 结合。体内实验验证了 AMSC 衍生的外泌体 miR-223-3p 可促进伤口愈合，并上调α-SMA、CD31、COL1A1、COL2A1、COL3A1，下调 MAPK10、TNF-α、IL-β 和 IL-6。
AMSC 衍生的外泌体 miR-223-3p 可能通过靶向 MAPK10 加速伤口愈合。
