NRP2不同表达状态对银屑病骨髓和皮肤间充质干细胞分化为血管内皮细胞的影响

项目名称： NRP2不同表达状态对银屑病骨髓和皮肤间充质干细胞分化为血管内皮细胞的影响

项目编号： No.81472888

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张开明

作者单位： 太原市中心医院

项目金额： 65万元

中文摘要： 真皮微血管增生扩张、通透性增高、对炎症细胞的粘附、渗透作用增强是银屑病皮损局部重要的发病特点。我们前期发现本病患者骨髓间充质干细胞（BMSCs）易于向血管内皮细胞（VEC）分化，进一步发现真皮MSCs（DMSCs）中与血管生成相关的基因表达异常，主要表现为VEGF协同受体如NRP2高表达、抑制血管生成基因如GATA-6低表达。MSCs在特定条件可分化为VEC，这一过程受VEGF信号通路调节。故我们推测，NRP2介导的VEGF信号可能在银屑病MSCs向VEC分化异常中起关键作用。因此，本研究拟体外干扰患者及对照骨髓和真皮MSCs的NRP2表达，将干扰后MSCs定向诱导为VEC，检测分化过程中VEGF信号通路的动态变化及分化后VEC的功能，且与患者皮损VEC比较，并构建NRP2-/-小鼠模型验证体外结果。课题将为解释银屑病MSCs为何易于向VEC分化提供理论依据，为银屑病血管研究提供新的方向。

中文关键词： 银屑病；间充质干细胞；NRP2；血管内皮细胞；动物模型

英文摘要： Hyperplasia and hyperpermeability of microvessel, increased adhesion and infiltration of inflammatory cells are main pathological characteristics of psoriatic lesion. We have previously found that bone marrow mesenchymal stem cells (BMSCs) derived from patients with psoriasis trend to differentiate into vascular endothelial cell (VEC), and those angiogenesis related genes such as vascular endothelial growth factor (VEGF) coreceptor Neuropilin 2（NRP2）、transcription factor GATA-6 are differently expressed in dermal MSCs（DMSCs）.MSCs are pluripotent stem cells and can be induced to differentiate into VEC under specific conditions. VEGF signaling pathway plays an important regulatory role in the differentiation of MSCs to VEC. So we speculate that the VEGF signaling pathway mediated by NRP2 may play a key role in the spontaneous VEC differentiation tendency of psoriatic MSCs.Therefore, the current study plan to interfere with the expression of NRP2 at BMSCs and DMSCs from patients and normal controls and then induced them to differentiate into VEC; detect the dynamic varitaion of VEGF signaling pathway during the differentiation process; and compare the function of induced VEC with those VEC separated form psoriatic lesions. The in vitro experiment will be confirmed by in vivo study using a NRP2-/- transgenic mice. The results of this study will provide a powerful explanation for why the BMSCs of patients with psoriasis tend to differentiate into VEC, and will lead a new direction of the vascular research of psoriasis.

英文关键词： psoriasis;mesenchymal stem cells;NRP2;vascular endothelial cell;animal model