Molecular Mechanisms of Insulin-like Growth Factor (IGF) Actions in Fish: Role of IGF Binding Protein-3

鱼类中胰岛素样生长因子 (IGF) 作用的分子机制：IGF 结合蛋白 3 的作用

• 批准号: 9728911
• 负责人: Cunming Duan
• 金额: $ 23.8万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9728911&HistoricalAwards=false
• 关键词: Molecular; Mechanisms; Insulin; like; Growth

9728911 Duan The proposed project involves studying the molecular mechanisms by which insulin-like growth factors (IGFs), peptide growth factors/hormones which are essential for normal growth and development, act to control embryonic tissue formation and differentiation in vivo. Recent studies utilizing cultured mammalian cells suggest that the bioactivity of IGFs could be modulated by specific, high-affinity IGF-binding proteins (IGFBPs) in vitro. The in vivo role of each IGFBP in controlling the availability of IGFs in specific embryonic tissues has not been determined. Research in this area has relied heavily on rodent models, and attempts have been hampered by the inaccessibility of the mammalian fetus which is enclosed in the uterus. In this project, Dr. Duan proposes to utilize a model teleost fish, the zebrafish (Danio rerio) to test the hypothesis that the access of IGFs to specific embryonic tissues is regulated by specific IGFBPs expressed locally and that this regulation is crucial for normal tissue growth and differentiation. The accessible, transparent and fast-developing embryos and the availability of numerous genetic mutants make zebrafish particularly suited for investigating the developmental role of IGFs/IGFBPs and the underlying mechanisms. The specific aims of the proposal are to: 1) determine the structure and biological activities of zebrafish IGFBP-3; 2) determine the developmental expression patterns of IGFBP-3 together with IGFs and the IGF-1 receptor; 3) determine the role of IGFBP-3 in controlling IGF actions in developing zebrafish embryos. The expected results should provide direct evidence for the in vivo role of IGFBP-3 in controlling IGF actions in a vertebrate embryo and will further our understanding of how the IGF system acts to control growth and development in vertebrates. Determination of the structures of fish IGFBP-3 and development of the corresponding protein, cDNA probe and antiserum will make available, for the first time, valuable tools for investigation of IGFBP actions in a teleost fish. Information gained from these studies may prove to be valuable to aquaculture for efficient production of animal protein to meet the needs of a continually growing human population.

拟建项目主要研究胰岛素样生长因子（IGFs）和肽生长因子/激素在体内控制胚胎组织形成和分化的分子机制，IGFs是正常生长发育所必需的肽生长因子/激素。最近利用培养的哺乳动物细胞进行的研究表明，igf的生物活性可以通过特异性的、高亲和力的igf结合蛋白（igfbp）在体外调节。每种IGFBP在体内控制特定胚胎组织中igf可用性的作用尚未确定。这一领域的研究在很大程度上依赖于啮齿动物模型，并且由于哺乳动物的胎儿被封闭在子宫内而无法接近，这一尝试受到了阻碍。在这个项目中，Duan博士建议利用模型硬骨鱼斑马鱼（Danio rerio）来验证igf进入特定胚胎组织的途径是由局部表达的特定igfbp调节的，这种调节对正常组织的生长和分化至关重要。易于获取、透明和快速发育的胚胎以及大量基因突变体的可用性使得斑马鱼特别适合研究igf / igfbp的发育作用及其潜在机制。该提案的具体目的是：1)确定斑马鱼IGFBP-3的结构和生物活性；2)确定IGFBP-3与igf及IGF-1受体的发育表达模式；3)确定IGFBP-3在斑马鱼胚胎发育过程中控制IGF的作用。预期结果将为IGFBP-3在脊椎动物胚胎中控制IGF作用的体内作用提供直接证据，并将进一步加深我们对IGF系统如何控制脊椎动物生长发育的理解。鱼类IGFBP-3的结构测定、相应蛋白、cDNA探针和抗血清的开发，将首次为研究IGFBP在硬骨鱼中的作用提供有价值的工具。从这些研究中获得的信息可能证明对水产养殖有效生产动物蛋白以满足不断增长的人口的需要是有价值的。