周细胞活化是肾间质纤维化进展关键事件。TGF-β、PDGF等多条“致纤维化信号通路”过度激活是周细胞活化发生和维系重要基础。我们前期创新性发现：①核心岩藻糖转移酶FUT8特异介导的蛋白质翻译后核心岩藻糖基化（CF）修饰是调控上述信号通路活性共同靶点；②骨髓间充质干细胞（BMSCs）外泌体可抑制CF修饰及周细胞活化，但机制不清。BMSCs外泌体可通过膜配体与靶细胞相互作用并传递microRNA。本项目采用活体成像、激光扫描共聚焦显微镜等研究静脉输注BMSCs及外泌体在体内分布时空特征，明确BMSCs作用方式；收集周细胞活化微环境下BMSCs外泌体，筛选调控FUT8表达的microRNA；采用多重标技术定量蛋白质组学，定位、聚类及蛋白间相互作用分析筛选与外泌体膜配体相结合的周细胞膜受体，以阐明BMSCs外泌体对周细胞活化的作用与机制，为干细胞外泌体治疗肾间质纤维化提供新理论依据及临床转化基础。

Pericytes activation is the key event in the process of renal interstitial fibrosis. The overactivated multiple fibrotic signaling pathways including TGF-β and PDGF pathways, are the key base for the initiation and the mantainence of pericytes activation. Our previous creative studies have found that posttranslational core fucosylation regulated specifically by fucosyltransferase 8 (FUT8) was the common target for the abovementioned multiple fibrotic signaling pathways. In addition, BMSCs (bone marrow derived mesenchymal stem cells) or its exosome could inhibit core fucosylation and pericytes activation in renal interstitial fibrosis. But the underlying mechanism remained unclalified. Exosome may interact with target cells by surface-expressed ligands to deliver microRNA. To clarify the action mode of BMSCs, the spatial and temporal distribution patterns of BMSCs or exosome after injection will be traced by in vivo imaging two-photon, microscopy. MicroRNA expression microarray will be used to analyze the candidate microRNA regulating the expression of FUT8 in BMSCs exosome exposed to the microenvironment of pericytes activation. Multiple labelled quantitative proteomics followed by localization, clustering and protein-protein interaction analyses will be used to screen the candidate exosome surface-expressed ligand mediating the interaction with surface-expressed receptor in pericytes. These study will clarify the effect and the underlying mechanism of BMSCs derived-exosome on pericytes activation. We believe that our findings will provide a new theory evidence for BMSCs therapy on renal interstitial fibrosis and a basis for clinical transformation.