miR-30a-5p介导肾病综合征足细胞损伤及机制研究

MiR-30a-5p was upregulated in puromycin aminonucleoside（PAN） rat renal tissue screened by microRNA chip.Our previous results showed that miR-30a-5p also increased in podocyte stimulated by PAN;Podocyte overexpressed miR-30a-5p displayed deffererentiation and foot process confluence,by bioinormatics analization and fluorescence report we found CD2AP was the target of miR-30a-5p.The CD2AP was downregulated at the same time of podocyte damaged,all that indicated CD2AP was associated with the miR-30a-5p induced podocyte injury.We aim at the following :to clarify the relation of miR-30a-5p and podocyte injury in vivo and in vitro,by lentivirus to overexpression or gene sliencing miR-30a-5p;to disclose the role that CD2AP played in podocyte injury;and to study the assoaciation between miR-30a-5p in renal of PAN rat and children and the clinical manifestation.This is the first investigation as so far in children and will offer the new method and new target for treatment of primary nephrotic syndrome in children.

miR-30a-5p是我们应用低密度芯片筛选发现的在嘌呤霉素肾病大鼠肾组织中表达显著上调的miRNA。前期发现：受损足细胞miR-30a-5p表达增加，miR-30a-5p过表达可致足细胞出现足突融合；生物信息学及荧光素酶报告基因检测CD2AP是miR-30a-5p的靶基因。我们则发现足细胞损伤的同时CD2AP表达下调，提示miR-30a-5p 致足细胞损伤的机制与CD2AP介导的生物学效应有关。本研究拟：在体及细胞培养方法观察miR-30a-5p过表达、表达沉默与足细胞损伤、CD2AP蛋白表达变化间的关系；以CD2AP为切入点，采用慢病毒介导的基因沉默和过表达技术，分析miR-30a-5p影响足细胞损伤的分子机制；并分析肾病大鼠及儿童肾组织miR-30a-5p表达与临床表现的相关性。miR-30a-5p影响足细胞损伤机制研究未见报道，本研究有源头创新性，可为儿童PNS的防治提供新线索。

miR-30a-5p是我们应用低密度芯片筛选发现的在嘌呤霉素肾病大鼠肾组织中表达显著上调的miRNA。前期发现：受损足细胞miR-30a-5p表达增加，miR-30a-5p过表达可致足细胞出现足突融合；生物信息学及荧光素酶报告基因检测CD2AP是miR-30a-5p的靶基因。我们则发现足细胞损伤的同时CD2AP表达下调，提示miR-30a-5p 致足细胞损伤的机制与CD2AP介导的生物学效应有关。本研究拟：在体及细胞培养方法观察miR-30a-5p过表达、表达沉默与足细胞损伤、CD2AP蛋白表达变化间的关系；以CD2AP为切入点，采用慢病毒介导的基因沉默和过表达技术，分析miR-30a-5p影响足细胞损伤的分子机制；并分析肾病大鼠及儿童肾组织miR-30a-5p表达与临床表现的相关性。miR-30a-5p影响足细胞损伤机制研究未见报道，本研究有源头创新性，可为儿童PNS的防治提供新线索。