内皮祖细胞外泌体中miRNA-222-3p对糖尿病小鼠皮肤伤口愈合的影响  

Effect of miR-222-3p in endothelial progenitor cell-derived exosomes on skin wound healing in diabetic mice

作　　者：王永琪 季华 唐颖 巫婷婷 揭茹艳 陈明卫[1] Wang Yongqi;Ji Hua;Tang Ying;Wu Tingting;Jie Ruyan;Chen Mingwei(Dept of Endocrinology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院内分泌科,合肥230022

出　　处：《安徽医科大学学报》2024年第7期1195-1200,共6页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金(编号:2108085MH269)。

摘　　要：目的了解内皮祖细胞外泌体(EPCs-Exo)中的miRNA-222-3p对糖尿病小鼠皮肤伤口愈合的影响。方法采用荧光染色法对C57BL/6小鼠骨髓来源内皮祖细胞(EPCs)进行鉴定。对从EPCs培养基中分离出的EPCs-Exo进行鉴定以及miRNA高通量测序。建立糖尿病小鼠皮肤损伤模型,随机分为5组:PBS组、EPCs-Exo组、空白组、agomiR-222-3p组、antagomiR-222-3p组。根据不同分组,连续处理14 d,观察创面愈合率,免疫荧光方法了解治疗前后创缘组织中活性氧(ROS)、血管内皮生长因子(VEGF)、CD31表达水平变化。结果EPCs-Exo促进糖尿病小鼠皮肤伤口愈合,降低创缘组织中ROS表达水平,增加VEGF、CD31表达水平(P<0.05)。高通量测序提示miRNA-222-3p在EPCs-Exo中高度表达。创缘组织局部皮下注射miRNA-222-3p可显著促进糖尿病小鼠皮肤伤口愈合,降低创缘组织中ROS表达水平,增加VEGF、CD31表达水平(P<0.05)。结论miRNA-222-3p促进糖尿病小鼠伤口愈合,在EPCs-Exo促进创面愈合过程中发挥重要作用。Objective To explore the effect of miRNA-222-3p in endothelial progenitor cell-derived exosomes(EPCs-Exo)on skin wound healing in diabetic mice.Methods Endothelial progenitor cell(EPCs)derived from C57BL/6 mouse bone marrow were identified by fluorescence staining.Subsequently,EPCs-Exo isolated from the media of EPCs were identified,and high-throughput sequencing of EPCs-Exo miRNA was completed.The skin injury model of diabetic mice was established.According to different groups,the wounds were treated with externally applied phosphate buffer solution(PBS)and EPCs-Exo;Subcutaneous injection of PBS,agomiR-222-3p,and antagomiR-222-3p at the edge of the wound was performed continuously for 14 days,and the wound healing rate was observed.Meanwhile,immunofluorescence methods were used to investigate the changes in the expression levels of ROS,CD31,and VEGF in the wound margin tissue before and after treatment.Results EPCs-Exo significantly accelerated skin wound healing in diabetic mice,reduced the level of ROS,and increased the expression level of VEGF and CD31 in the wound margin tissue(P<0.05).High-throughput sequencing showed that miRNA-222-3p was highly expressed in EPCs-Exo.Local subcutaneous injection of miRNA-222-3p into wound margin tissue significantly promoted the skin wound healing of diabetic mice,reduced the level of ROS,and increased the expression level of VEGF and CD31 in the wound margin tissue(P<0.05).Conclusion MiRNA-222-3p promotes wound healing in diabetic mice and plays an important role in EPCs-Exo promoting wound healing.

关 键 词：内皮祖细胞 外泌体 糖尿病足 miRNA-222-3p 创面愈合 

分 类 号：R589.9[医药卫生—内分泌]