HucMSC外泌体转运miR-13474调控CPEB2促进糖尿病足创面修复的研究

糖尿病足（DFU）创面迁延不愈问题是临床难题。我们研究发现脐带间充质干细胞外泌体（hucMSC-Ex）能够促进其创面愈合和组织再生，表明hucMSC-Ex在DFU治疗中具有较好临床应用潜力。经miRNA测序筛选出hucMSC-Ex中高表达全新miRNA分子NC_000019.10_13474（miR-13474），抑制外泌体内miR-13474表达显著减弱了其修复效果。进一步发现miR-13474可能通过靶向抑制RNA结合蛋白CPEB2，进而影响CPEB2下游分子表达和信号通路转导，但确切靶细胞及分子机制待阐明。因此，本研究拟采用ROSA26-LSL-EGFP转基因小鼠等模型明确hucMSC-Ex修复DFU的主要作用靶细胞；采用转录组测序、IPA机制分析等技术确定CPEB2调控效应及下游互作网络，揭示确切修复机制。在此基础上构建miR-13474工程化外泌体，为DFU治疗提供新方案。

Diabetic foot ulcer is still lacking effective therapeutics for the delayed healing process，which remains to be a difficult clinical problem. We found that hucMSC derived exosomes (hucMSC-Ex) observably promote the diabetic wound healing and tissue regeneration, which presents a promising application potential. We next screened out a brand new miRNA, NC_000019.10_13474 (miR-13474) with an extremely high differential expression between hucMSC-Ex and HFL1-Ex by miRNA sequencing. Deletion of miR-13474 from hucMSC-Ex significantly receded its repairing effect on DFU. Further study showed that miR-13474 probably regulating target cell biological function by combination and inhibition of CPEB2, which is a highly conserved RNA binding protein. However, the down-stream target molecule of CPEB2 and signaling transduction as well as the definite target cell remains to be discovered. Therefore, we are going to explore main target cell by using ROSA26-LSL-EGFP transgenic mice model and uncover its response mechanism by using transcriptome sequencing combing with IPA bioinformatics analysis. Furthermore, we plan to establish a miR-13474 modified hucMSC-Ex and make efforts to provide a new therapeutic strategy for DFU clinical treatment.