Analysis of miR-203a-3p/SOCS3-mediated induction of M2 macrophage polarization to promote diabetic wound healing based on epidermal stem cell-derived exosomes

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

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作者:Hao Yang, Hailin Xu, Zhiyong Wang, Xiaohui Li, Peng Wang, Xiaoling Cao, Zhongye Xu, Dongming Lv, Yanchao Rong, Miao Chen, Bing Tang, Zhicheng Hu, Wuguo Deng, Jiayuan Zhu

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.

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.

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.

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