MATERNAL GROWTH FACTORS IN NEONATAL GROWTH

新生儿生长中的母亲生长因素

• 批准号: 3448400
• 负责人: FRANK ALBERT SIMMEN
• 金额: $ 4.93万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3448400
• 关键词: autoradiography; cell differentiation; cell population study; colostrums; complementary DNA; enzyme linked immunosorbent assay; gel electrophoresis; gel filtration chromatography; gene expression; growth /development; growth factor; high performance liquid chromatography; immunoprecipitation; ion exchange chromatography; lactation; milk; molecular cloning; newborn animals; nucleic acid sequence; organ culture; peptide hormone; radiotracer; tissue /cell culture

Recent evidence in the literature indicates that the milk of lactating mammals contains polypeptide growth factors which are capable of stimulating the proliferation of animal cells in vitro. The presence of relatively high concentrations of mitogenic activities in mammary secretions raises a number of important questions with regard to their identify, structure, synthesis, secretion and possible involvement in the early development of the neonate. The aim of this proposal is to use the domestic pig, Sus domesticus, for an examination of growth promoting activities in mammary secretions and their biological effects in the newborn animal. The pig was chosen for these experiments since it undergoes marked physiological changes early in life, many of which are clearly dependent on the suckling process. For example, early growth and maturation of the intestinal epithelium in the newborn pig is dependent upon epithelial cell proliferation, perhaps stimulated in part by ingested factors. In addition, large amounts of colostrum can be obtained from lactating animals and will serve as the starting material for growth factor isolation. Virtually nothing is known at present concerning the nature of growth promoting activities in porcine mammary secretions. Therefore, initial experiments will attempt to identify and characterize these mitogenic activities. In turn, an appropriate immunological or receptor based assay will be developed for measurement of the factor in mammary secretions and maternal tissues. Once the nature of these polypeptides is established, then attempts will be made to isolate and characterize their corresponding gene(s) using recombinant DNA techniques. The temporal and tissue-specific patterns of expression of the gene will also be determined for both maternal and neonatal sources. The final aspect of the study will involve cloning of the gene in a bovine papilloma virus-derived vector followed by transfection into murine C127 cells. This experiment should result in the production of relatively large quantities of the factor in cell culture. This material will then be utilized for physiological studies in the neonate. It is hoped that a study of growth promoting activities in mammary secretions will contribute towards a further understanding of what the roles of polypeptide growth factors are in vivo and how their expression relates to early postnatal growth. These studies should have a direct relevance to human infant nutrition.

最近文献中的证据表明， 哺乳动物含有能够 在体外刺激动物细胞的增殖。 的存在 在乳腺中相对高浓度的促有丝分裂活性 秘书处提出了一些重要问题， 鉴定、结构、合成、分泌和可能参与 新生儿的早期发育。 这项建议的目的是利用家猪，猪， 乳腺分泌物中的促生长活性及其 对新生动物的生物学影响。 猪被选中是为了这些 因为它在生命早期经历了显著的生理变化， 其中许多明显依赖于哺乳过程。 比如说， 新生猪小肠上皮的早期生长和成熟 依赖于上皮细胞增殖，可能部分刺激了 通过摄入的因素。 此外，大量的初乳可以 从泌乳动物中获得，并将作为 生长因子分离。 事实上，目前还没有任何关于 猪乳腺分泌物中促生长活性的性质。 因此，最初的实验将试图识别和表征 这些有丝分裂活动。 反过来，适当的免疫或 基于受体的测定将被开发用于测量 乳腺分泌物和母体组织。 一旦这些的性质 多肽建立后，将尝试分离和 使用重组DNA技术表征其相应的基因。 基因表达的时间和组织特异性模式将 也可以确定产妇和新生儿的来源。 最终 这项研究的一个方面将涉及克隆牛乳头状瘤中的基因 病毒衍生的载体，随后转染入鼠C127细胞。 这 实验应该导致相对大量的生产 在细胞培养中的作用。 这些材料将用于 新生儿的生理学研究。 人们希望， 促进乳腺分泌物中的活性将有助于 进一步了解多肽生长因子的作用 以及它们的表达与出生后早期生长的关系。 这些 研究应与人类婴儿营养直接相关。