携miRNA-21间充质干细胞外泌体调控肾小管上皮细胞自噬并减轻慢性肾损伤的机制研究

间充质干细胞（MSCs）对多种肾脏疾病模型具有良好的治疗效果，阐明其作用机制有助于更好地将干细胞治疗推广到临床应用。课题组前期研究发现脐带间充质干细胞外泌体（hucMSC-Ex）通过高表达miRNA-21减轻肾小管上皮细胞损伤，但其起效的具体机制尚不清楚。新近研究提示miRNA-21显著抑制自噬进程，且自噬水平的变化与细胞损伤密切相关。因此，我们推测：hucMSCs分泌携带miRNA-21信号的外泌体被肾小管上皮细胞接收后，可能通过调控细胞内自噬水平，从而减轻细胞损伤。本课题拟建立hucMSC-Ex与大鼠肾小管上皮细胞（NRK-52E）共培养体系以及肾脏损伤模型，采用基因干扰、自噬调控及动物实验等方法，阐明hucMSC-Ex通过细胞间信息传递减轻肾小管上皮细胞损伤的分子机制，为临床干细胞治疗肾脏疾病提供理论依据。

Mesenchymal stem cells (MSCs) are fairly effective in the treatment of a variety of kidney disease models, and to clarify the therapeutic mechanism helps to apply MSCs to a safe and effective clinical treatment. Our preliminary experiments showed that exosomes secreted by human umbilical cord MSCs (hucMSC-Ex) were abundant in miR-21, which can ameliorate renal tubular epithelial cell injury, but the mechanism is not clear. Recent studies suggest that miRNA-21 significantly inhibits autophagy progress and the autophagy level is closely associated with cell injury. Thus we hypothesize that hucMSCs secrete exosomes carrying miRNA-21 can be absorbed by renal tubular epithelial cells and further attenuate cells injury by regulating autophagy. In this study, co-culture of hucMSC-Ex and rat renal tubular epithelial cells (NRK-52E), and kidney injury animal model are established. Furthermore, experimental techniques of gene interference, autophagy regulation and animal experiments are to be used to clarify the molecular mechanism that hucMSC-Ex ameliorate renal tubular epithelial cell injury by intercellular information transmission, which will provide a clinically theoretical basis for stem cell treatment in kidney diseases.