Foxd1阳性的后肾间充质细胞通过外泌体miR-874抑制MAPK通路改善系膜增生性肾小球肾炎的机制研究

系膜增生性肾小球肾炎（MsPGN）是我国慢性肾脏病/终末期肾病的重要病因，目前尚无理想的治疗方法。在肾脏发育过程中，系膜细胞是由Foxd1阳性的后肾间充质细胞发育而来，我们前期发现Foxd1阳性的后肾间充质细胞能够促进系膜损伤修复、稳定系膜正常的结构和功能治疗MsPGN，同时其分泌的外泌体可抑制PDGF-BB诱导的系膜细胞增殖。由于细胞可通过外泌体携带microRNA介导细胞间通讯，且预实验提示Foxd1阳性的后肾间充质细胞外泌体携带miRNA-874可调控系膜细胞增殖重要通路MAPK通路，基于此，本项目将进一步在体内和体外明确Foxd1阳性的后肾间充质细胞外泌体对系膜细胞增殖的作用，并深入探究Foxd1阳性的后肾间充质细胞外泌体携带microRNAs通过作用靶基因/通路抑制系膜细胞增殖的具体分子机制，为MsPGN的干预/治疗及外泌体临床应用提供依据。

Mesangial proliferative glomerulonephritis (MsPGN) is the major cause of chronic kidney disease/ end-stage renal disease in China, and there is no ideal therapy. During kidney development, the mesangial cells are developed from Foxd1+ metanephric mesenchyme cells. In previous work, we found that as the progenitor cells of mesangial cells, Foxd1+ mesangial precursor cells could stabilize the structure and function of mesangial cells that had undergone pathological changes via multiple pathways, and Foxd1+ metanephric mesenchyme cells-derived exosomes could inhibit mesangial cells proliferation induced by PDGF-BB. Since cells-derived exosomes could mediate cell communication by carrying microRNAs，and preliminary experiments showed that Foxd1+ metanephric mesenchyme cells-derived exosomes could carry miRNA-874, which might regulate the MAPK pathway that is the key pathway involved in mesangial cell proliferation. Thus, this project is aiming to clarify the effect of Foxd1+ metanephric mesenchyme cells-derived exosomes on mesangial cell proliferation in vivo and in vitro, and to explore the molecular mechanism of Foxd1+ metanephric mesenchyme cells-derived exosomes carrying miRNAs inhibiting mesangial cell proliferation via regulating target genes/pathways, which can provide theoretical foundation for the intervention/therapeutic target of MsPGN and clinical application of Foxd1+ metanephric mesenchyme cells-derived exosomes.