IGFBP-3酶解片断1-98和1-212的IGF非依赖性作用及其在BMP信号通路中的作用研究

项目名称： IGFBP-3酶解片断1-98和1-212的IGF非依赖性作用及其在BMP信号通路中的作用研究

项目编号： No.31200877

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生理学与整合生物学

项目作者： 钟英斌

作者单位： 苏州大学

项目金额： 24万元

中文摘要： IGFBP-3是一种多功能蛋白，既有IGF依赖性和也有IGF非依赖性作用。申请人研究发现IGFBP-3的IGF非依赖性作用之一是通过结合BMP配体、抑制BMP信号的转导来实现。人体内存在两种天然的IGFBP-3的酶解片断1-98和1-212，它们与IGF结合能力有所减弱，但它们是否具有IGF非依赖性作用以及是否与BMP信号通路有关还不清楚。本项目将在PC-3细胞中研究两种IGFBP-3酶解片断的IGF非依赖性作用，用Ligand印迹确定这两种酶解片断与BMP配体的结合能力，在U2OS细胞以及模式动物斑马鱼中研究两种IGFBP-3酶解片断体外和体内对BMP信号转导的作用，比较IGFBP-3两种酶解片断与完整片断三者之间的功能异同。最终解析IGFBP-3酶解片断生理功能和作用机制。本项目的研究对我们进一步了解IGFBP-3的作用机制，以及IGFBP-3在临床上用于疾病的诊断和治疗具有指导意义。

中文关键词： IGF；IGF依赖性作用；IGF非依赖性作用；IGFBP-3酶解片断；斑马鱼

英文摘要： Genetic and clinical research observations suggest that the insulin-like growth factor (IGF) signaling pathway plays a fundamental role in regulating animal growth and development as well as in maintaining adult homeostasis. IGF binding protein-3 (IGFBP-3) is the major binding protein of IGFs in the bloodstream. IGFBP-3 is a multiple functional protein that has IGF-dependent and -independent actions in cultured mammalian cells. It has become widely appreciated that IGF-independent actions of IGFPB-3 contribute to improving the pathophysiology of human desease, such as cancer, diabetes, and malnutritions. Previously, we found that IGFBP-3 exerts its IGF-independent function by antagonizing BMP signaling in vitro and in vivo. Interestingly, two IGFBP-3 fragments, 1-98 and 1-212, were isolated from human hemofiltrate, and found that they have reduced IGF binding activity. But whether they have IGF-independent action and whether the can antagonizing BMP signaling in vitro and in vivo are still unknown. In this study, the IGF bind domain of IGFBP-3 fragment 1-98 and 1-212 will be mutated. The IGF- - independent action of the two fragments will be studied on PC-3 cells by determining the pro-apoptotic activities. The BMP ligand binding activity of the two fragments will be tested by ligand blotting. The in vitro and i

英文关键词： Insulin-like growth factor；IGF-dependent action；IGF-independent action；IGFBP-3 fragment；zebrafish