Yang Hao, Xu Hailin, Wang Zhiyong, Li Xiaohui, Wang Peng, Cao Xiaoling, Xu Zhongye, Lv Dongming, Rong Yanchao, Chen Miao, Tang Bing, Hu Zhicheng, Deng Wuguo, Zhu Jiayuan
First Affiliated Hospital of Sun Yat-sen University, Department of Burn and Wound Repair, Guangzhou, China.
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
Diabetes Res Clin Pract. 2023 Mar;197:110573. doi: 10.1016/j.diabres.2023.110573. Epub 2023 Feb 8.
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.
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.
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.
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.
开发针对个体糖尿病患者改善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景的纳米材料，并且可以从中分离出微小RNA（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。
采用qPCR、流式细胞术和蛋白质免疫印迹法来验证表皮干细胞衍生外泌体（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-EXOs中靶向SOCS3的关键miRNA，我们在体外验证了其机制。最后，使用动物模型验证促进愈合的效果。
使用EpiSC-EXOs可降低SOCS3表达并促进M2巨噬细胞极化。EpiSC-EXOs中存在的丰富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激动剂处理db/db小鼠伤口模型具有促愈合作用。
我们的结果表明，EpiSC-EXOs中存在的丰富miR-203a-3p可通过下调SOCS3促进M2巨噬细胞极化，并表明糖尿病伤口可通过该机制获得更好的愈合效果。
