SDF-1/CXCR7信号轴对内皮祖细胞纤维变（Endo-MT）和脉络膜纤维化的影响及其机制研究

项目名称： SDF-1/CXCR7信号轴对内皮祖细胞纤维变（Endo-MT）和脉络膜纤维化的影响及其机制研究

项目编号： No.81470637

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： 袁非

作者单位： 复旦大学

项目金额： 73万元

中文摘要： 脉络膜新生血管（CNV）最常见于AMD和病理性近视，至今尚无有效的治愈方法。CNV 病灶的纤维化将导致感光细胞死亡，是致盲的直接原因之一。我们前期研究发现阻断CXCR4受体功能，将促进CNV发生纤维化。本申请课题拟运用内皮（祖）细胞分离和培养技术，通过CXCR7特异受体拮抗剂和基因沉默等手段，全面系统地观察CXCR7 分子对内皮（祖）细胞增殖、黏附、迁移、管腔形成、Endo-MT以及纤维化的影响。进一步采用CNV动物模型，明确CXCR7+内皮（祖）细胞在CNV纤维化形成中的作用及其分子机制。本项目的预期成果将为研发基于CXCR7为分子靶点的CNV治疗新药以及开展抗VEGF和抗CXCR7联合治疗提供新思路并积累资料。

中文关键词： 新生血管；SDF-1；纤维化

英文摘要： Choroidal neovascularization (CNV) is most common in age related macular degeneration (AMD) and pathologic myopia, which can lead to irreversible blindness because of the formation of fibrosis resulting from the death of photoreceptor cells, with no effective cure yet. My previous study found that blocking CXCR4 receptor will promote formation of fibrosis in CNV. This project aim to use the endothelial progenitor cells (EPCs) in vitro, by means of gene silencing and antagonist intervention, to understand the CXCR7 expression at the mRNA and protein levels and cell surface molecules, and the role of CXCR7 on PECs biology function such as proliferation, adhesion, migration and tube formation, the role of biological behavior and the its possible impact of endothelial-to-mesenchymal transition (Endo-MT). In vivo study, an animal model of CNV was induced by laser photocagulation, and then we use a variety of molecular biology methods to explore the interaction between CXCR7 and vascular endothelial cells, and the pathogenic role of CXCR7 on the formation of fibrosis in CNV. The results of this project will provide strong scientific evidences for developing of new drugs targeting CXCR7 to prevent blindness caused by fibrosis in CNV.

英文关键词： neovascularization;SDF-1;fiblosis