Background

The development of therapeutic strategies to improve wound healing in individual diabetic patients remains challenging. Stem cell-derived exosomes represent a promising nanomaterial, and microRNAs (miRNAs) can be isolated from them. It is important to identify the potential therapeutic role of specific miRNAs, given that miRNAs can play a therapeutic role.

Methods

qPCR, flow cytometry, and western blotting were used to verify the effect of epidermal stem cell-derived exosomes (EpiSC-EXOs) on M2 macrophage polarization and SOCS3 expression. By screening key miRNAs targeting SOCS3 in EpiSC-EXOs by high-throughput sequencing, we verified the mechanism in vitro. Finally, an animal model was used to verify the effect of promoting healing.

Results

The use of EpiSC-EXOs reduced SOCS3 expression and promoted M2 macrophage polarization. The abundant miR-203a-3p present in the EpiSC-EXOs specifically bound to SOCS3 and activated the JAK2/STAT3 signaling pathway to induce M2 macrophage polarization. Treatment of the db/db mouse wound model with miR-203a-3p agomir exerted a pro-healing effect.

Conclusions

Our results demonstrated that the abundant miR-203a-3p present in EpiSC-EXOs can promote M2 macrophage polarization by downregulating SOCS3 and suggested that diabetic wounds can obtain better healing effects through this mechanism.

中文翻译：

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基于表皮干细胞来源的外泌体分析 miR-203a-3p/SOCS3 介导的 M2 巨噬细胞极化诱导促进糖尿病伤口愈合

背景

开发改善个体糖尿病患者伤口愈合的治疗策略仍然具有挑战性。干细胞衍生的外泌体是一种很有前途的纳米材料，可以从中分离出 microRNA (miRNA)。鉴于 miRNA 可以发挥治疗作用，确定特定 miRNA 的潜在治疗作用很重要。

方法

qPCR、流式细胞术和蛋白质印迹法用于验证表皮干细胞来源的外泌体 (EpiSC-EXOs) 对 M2 巨噬细胞极化和 SOCS3 表达的影响。通过高通量测序筛选 EpiSC-EXO 中靶向 SOCS3 的关键 miRNA，我们在体外验证了该机制。最后通过动物模型验证促进愈合的效果。

结果

EpiSC-EXO 的使用降低了 SOCS3 的表达并促进了 M2 巨噬细胞的极化。EpiSC-EXO 中存在的大量 miR-203a-3p 特异性结合 SOCS3 并激活 JAK2/STAT3 信号通路以诱导 M2 巨噬细胞极化。用 miR-203a-3p agomir 处理 db/db 小鼠伤口模型发挥了促愈合作用。

结论

我们的研究结果表明，存在于 EpiSC-EXO 中的丰富的 miR-203a-3p 可以通过下调 SOCS3 促进 M2 巨噬细胞极化，并表明糖尿病伤口可以通过这种机制获得更好的愈合效果。