MECHANISMS OF ANGIOGENESIS IN THE FETUS AND NEWBORN

胎儿和新生儿的血管生成机制

• 批准号: 3473673
• 负责人: PETER G MILNER
• 金额: $ 11.28万
• 依托单位: JEWISH HOSPITAL OF SAINT LOUIS
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-01-29 至 1992-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3473673
• 关键词: SDS polyacrylamide gel electrophoresis; angiogenesis; angiogenesis factor; autoradiography; blood vessels; chemical binding; cow; cytokine; developmental genetics; embryo /fetus; embryo /fetus cell /tissue; gene expression; heart; high performance liquid chromatography; immunoprecipitation; in situ hybridization; laboratory rat; mammalian embryology; messenger RNA; newborn animals; northern blottings; radionuclides; receptor binding; retinoids; scintillation counter; tissue /cell culture; vitamin analog

The Principal Investigator recently discovered, purified, and cloned and sequenced a novel 18 kD mitogenic protein from bovine uterus which is closely related to, but distinct from bFGF. This growth factor, termed pleiotrophin (PTN) or heparin-binding growth factor (HBGF)-8, displays extraordinary conservation of cDNA sequence between 3 mammalian species and is widely expressed and developmentally regulated in the fetus and newborn. Following birth, the levels of this growth factor decline dramatically. cDNA cloning indicate the relationship between PTN and the MK gene, a recently described retinoic acid induced gene of unknown function identified in differentiating teratocarcinoma cells. Thus, PTN and MK are thought to be the first members of a new family of developmentally regulated cytokines active in the tissue of fetal and developing mammals. Preliminary data by the Principal Investigator demonstrate that the pure bovine PTN protein may be angiogenic since it stimulates 3H-thymidine uptake into cultures of fetal bovine heart endothelial cells. The aim of the studies described in this grant proposal is to investigate if PTN mRNA is expressed in developing vascular structures such as the heart and blood vessels of the mammalian fetus and newborn, and whether this expression is developmentally regulated. Studies will also be performed to confirm the mitogenic effects of PTN on various cell types of developing blood vessels and heart. The role of Vitamin A in blood vessel development will be studied. The Principal Investigator also aims to identify the cell surface on responsive vascular cells which mediates the angiogenic effect of PTN, and to purify this receptor. Detailed investigation of the role of PTN in development and enlargement of vascular structures will, when complete, identify important mechanisms of angiogenesis in the developing mammal and also have bearing on regional vascular malformations.

主要研究人员最近发现，纯化和克隆， 测序了一种从牛子宫的新型促丝裂蛋白 与BFGF密切相关，但与BFGF不同。 这个生长因子称为 pleiotiotrophin（PTN）或肝素结合生长因子（HBGF）-8，显示 三种哺乳动物物种之间的cDNA序列的非凡保护 并在胎儿中得到广泛表达和发育监管 新生。 出生后，这种生长因素的水平下降 急剧。 cDNA克隆表示PTN与 MK基因，最近描述的视黄酸诱导的未知基因 在分化的畸胎卡诺瘤细胞中鉴定出的功能。 因此，PTN 和MK被认为是新家庭的第一批成员 发育调节的细胞因子活跃于胎儿组织中 发展哺乳动物。 主要研究者的初步数据 证明纯牛PTN蛋白可能是血管生成的 刺激3H-胸腺苷吸收到胎牛心脏的培养物中 内皮细胞。 这笔赠款中描述的研究的目的 提案是在开发中调查PTN mRNA是否表达 哺乳动物的心脏和血管等血管结构 胎儿和新生儿，以及这种表达是否在发展上 受监管。 还将进行研究以确认有丝分裂 PTN对各种细胞发育中的血管的影响， 心。 维生素A在血管发育中的作用将是 研究。 主要研究者还旨在识别细胞 表面在反应性血管细胞上介导了血管生成作用 ptn的，并净化该受体。 对角色的详细调查 PTN在发育和扩大血管结构时，将于 完整，确定在发育中的血管生成的重要机制 哺乳动物，还与区域血管畸形有关。