Exploring the physiological, morphological and molecular bases of renal developmental programming.

探索肾脏发育规划的生理、形态和分子基础。

• 批准号: nhmrc : 384207
• 负责人: Prof John Bertram
• 金额: $ 28.16万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/exploring-physiological-morphological-developmental-programming/99631
• 关键词: Exploring; physiological; morphological; molecular; bases

Suboptimal fetal and neonatal development increases our risk of developing a range of diseases in adulthood. The concept that deleterious events during development can influence adult health is termed 'developmental programming'. Obtaining A Healthy Start to Life is a priority research goal of the Australian Government. The kidneys are particularly susceptible to developmental programming. This is in part because the functional units (nephrons) of the kidneys are all formed before birth in humans. Thus, if fetal development is suboptimal, babies are at risk of being born with a permanent nephron deficit, with functional and disease consequences. We have shown in male rats that the offspring of a maternal low protein diet have fewer nephrons and lower blood pressure than rats fed a normal diet. These rats display a striking sensitivity in adulthood to the feeding of a high salt diet. We will define the physiological and morphological bases of this sensitivity, and repeat these studies in females, as increasing evidence shows significant sex differences in developmental programming. Defining the molecular mechanisms of developmental programming is the greatest challenge for researchers in the field. We have recently completed the most comprehensive analysis to date of gene expression in the developing mouse kidney, and have shown for the first time that the mouse programmes kidney development. We will use the new techniques of genomics and bioinformatics to study the molecular mechanisms of kidney programming. This mechanistic data will provide an excellent hypothesis engine for future studies on the specific roles of these molecular pathways in developmental programming in all mammalian species.

胎儿和新生儿发育不佳会增加我们成年后罹患一系列疾病的风险。发育过程中的有害事件会影响成人健康的概念被称为“发育规划”。获得健康的生活开端是澳大利亚政府的优先研究目标。肾脏特别容易受到发育规划的影响。这在一定程度上是因为人类肾脏的功能单位(肾单位)都是在出生前形成的。因此，如果胎儿发育不佳，婴儿出生时就有可能患有永久性肾单位缺陷，从而导致功能和疾病后果。我们已经在雄性大鼠身上表明，与正常饮食的大鼠相比，母亲低蛋白饮食的后代拥有更少的肾单位和更低的血压。这些大鼠在成年后对高盐饮食表现出惊人的敏感性。我们将定义这种敏感性的生理和形态基础，并在女性身上重复这些研究，因为越来越多的证据表明，在发育规划方面存在显著的性别差异。确定发育编程的分子机制是该领域研究人员面临的最大挑战。我们最近完成了迄今为止对发育中的小鼠肾脏中基因表达的最全面的分析，并首次表明小鼠参与了肾脏的发育。我们将利用基因组学和生物信息学的新技术来研究肾脏编程的分子机制。这一机制数据将为未来研究这些分子途径在所有哺乳动物的发育规划中的具体作用提供一个很好的假说引擎。