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
王永琪 1季华 1唐颖 1巫婷婷 1揭茹艳 1陈明卫1
作者信息
- 1. 安徽医科大学第一附属医院内分泌科,合肥 230022
- 折叠
摘要
目的 了解内皮祖细胞外泌体(EPCs-Exo)中的miR-NA-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.
Abstract
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 ap-plied phosphate buffer solution(PBS)and EPCs-Exo;Subcutaneous injection of PBS,agomiR-222-3p,and an-tagomiR-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 ac-celerated 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 signifi-cantly 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Key words
endothelial progenitor cells/exosome/diabetic foot/miRNA-221-3 p/wound healing引用本文复制引用
基金项目
安徽省自然科学基金(2108085MH269)
出版年
2024
国家科技期刊平台
NSTL
万方数据