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

• 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

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，身体的许多主要器官获得了子宫外生活所必需的许多功能。在生命的这些早期阶段对生长的影响可能对成年人的健康产生深远的影响。大多数决定最终体重和功能的事件都是由血液中发现的蛋白质控制的。这种因子被称为胰岛素生长因子-1（IGF 1）。传统知识表明，该因子是在肝脏中响应生长激素（GH）信号而产生的。我们认为，这不是整个图片和另一个因素？细胞因子刺激因子1（CSF 1）-由称为巨噬细胞的免疫细胞产生，有助于控制GH/IGF-1系统，从而有助于控制出生后的生长。我们的数据表明，缺乏CSF 1功能的动物与GH/IGF-1缺乏的动物一样，具有一系列发育和生长异常。尽管我们的初步数据令人信服，但挑战仍然是了解这些不同因素如何相互作用以控制增长。有了这些知识，我们将能够更好地评估克服生长障碍的战略。为了实现这些目标，我们的目标是在大鼠中开发新的转基因技术。具体来说，我们将确定减少CSF 1信号对生长的影响以及提高CSF 1水平作为生长受损的可能治疗的有益影响。