CSF1 and the control of postnatal growth and organ development in the rat

CSF1 与大鼠出生后生长和器官发育的控制

基本信息

批准号：
G0901193/1
负责人：
David Hume
金额：
$ 82.85万
依托单位：
University of Edinburgh
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2010
资助国家：
英国
起止时间：
2010 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=G0901193%2F1
关键词：
CSF1 control postnatal growth organ

项目摘要

During pregnancy, many major organs of the body gain the many functions that will be necessary for life outside of the womb. Effects on growth at these early stages of life can have profound consequences for adult health. Most of the events that determine final body mass and function are controlled by protein found circulating in blood. This factor is called Insulin Growth Factor-1 (IGF1). Traditional knowledge indicates that this factor is made in the liver in response to growth hormone (GH) signals. We propose that this is not the entire picture and another factor ? Cytokine Stimulating Factor 1 (CSF1) - produced by the immune cells called macrophages contribute to the control the GH/IGF-1 system and thus contribute to the control of postnatal growth. We base this hypothesis on our data indicating that animals which lack CSF1 function have a range of developmental and growth abnormalities in common to animals deficient in GH/IGF-1. Although our preliminary data is compelling, the challenge remains to understand how these various factors interact to control growth. With this knowledge we will be better able to evaluate strategies to overcome growth impairment. To address these goals we aim to exploit new transgenic technologies in the rat. Specifically we will determine the consequence of reducing CSF1 signalling on growth and beneficial effects of elevating CSF1 levels as a possible treatment of impaired growth.

在怀孕期间，许多体内的主要器官都会获得许多在子宫外生活所必需的功能。在生活的这些早期阶段对生长的影响可能会对成人健康产生深远的影响。确定最终体重和功能的大多数事件都由发现血液循环的蛋白质控制。该因子称为胰岛素生长因子1（IGF1）。传统知识表明，该因素是根据生长激素（GH）信号在肝脏中产生的。我们建议这不是整个图片，也不是另一个因素？由称为巨噬细胞产生的免疫细胞产生的细胞因子刺激因子1（CSF1）有助于控制GH/IGF -1系统，因此有助于控制产后生长。我们基于我们的数据，这一假设表明缺乏CSF1功能的动物具有一系列发育和生长异常，因为动物缺乏GH/IGF-1的动物。尽管我们的初步数据令人信服，但挑战仍然是了解这些各种因素如何相互作用以控制增长。有了这些知识，我们将更好地评估克服增长障碍的策略。为了解决这些目标，我们旨在利用大鼠中的新转基因技术。具体而言，我们将确定减少CSF1信号传导对升高CSF1水平的生长和有益影响的结果，以作为对生长受损的可能治疗。