PDGF Receptor Signaling in Mammalian Development

哺乳动物发育中的 PDGF 受体信号传导

基本信息

  • 批准号:
    8054872
  • 负责人:
  • 金额:
    $ 39.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-04-01 至 2012-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Cardiovascular disease is one of the leading causes of death in the US, and the inability to repair damaged muscle is a major obstacle in treating heart disease. Currently, there are no definitive methods to improve heart function after a heart attack, and a common result is permanent muscle loss. While a significant amount of research has focused on the ability to expand or generate cardiomyocytes for replacement of the damaged tissue, less focus has been placed on controlling the detrimental effects of fibrosis and enhancing the beneficial effects of angiogenesis. Additional information on the epicardium, or outer layer of the heart, may provide insights into these processes. Studies have demonstrated that epicardial cells differentiate into cardiomyocytes, vascular smooth muscle cells, endothelial cells, and fibroblasts, and an in depth knowledge of the mechanisms that cause these cell populations to form in the embryonic heart will be essential for programming the adult epicardium to generate these cell types after heart injury. Platelet derived growth factor (PDGF) signaling pathways are essential for normal epicardial development, and the main goal of this proposal is to discover how PDGFs direct epicardial cell development and differentiation. This goal will be accomplished using epicardial-specific loss-of-function alleles of the PDGF receptors in the mouse. The specific aims of this proposal are: 1) To determine the mechanism of PDGF receptor action in the initial development of the epicardium; 2) To elucidate the requirement for PDGFR2 in coronary vascular smooth muscle cells and cardiac fibroblasts; and 3) To determine if PDGFR1 signaling is required for fibroblast development and function within the heart. Understanding the mechanisms of PDGF receptor function in the epicardium and epicardial derived cells will provide important insights into the signaling mechanisms governing epicardial cell biology and potentially reveal signaling pathways that could be manipulated to control fibrosis and direct angiogenesis after cardiac injury. PUBLIC HEALTH RELEVANCE: Cardiac fibrosis and impaired coronary artery function are two major features of heart disease, but few drugs or therapies have been identified that act upon the cells responsible for these problems. The goal of this research is to identify signals that can alter the formation and function of these cell types. Manipulation of these signals could improve the outcomes of cardiac injury. The success of these studies will provide information to advance the treatments used in repairing damaged hearts and reducing fibrosis.
描述(由申请人提供):心血管疾病是美国的主要原因之一,而无法修复受损的肌肉是治疗心脏病的主要障碍。目前,尚无确定的方法可以改善心脏病发作后的心脏功能,常见的结果是永久性肌肉损失。虽然大量研究集中在扩展或生成心肌细胞以替换受损组织的能力上,但很少关注控制纤维化的有害影响和增强血管生成的有益影响。有关心外膜或心脏外层的其他信息可能有助于深入了解这些过程。研究表明,心外膜细胞分化为心肌细胞、血管平滑肌细胞、内皮细胞和成纤维细胞,深入了解导致这些细胞群在胚胎心脏中形成的机制对于在心脏损伤后对成人心外膜进行编程以生成这些细胞类型至关重要。血小板衍生生长因子(PDGF)信号通路对于正常心外膜发育至关重要,该提案的主要目标是发现PDGF如何指导心外膜细胞发育和分化。这一目标将通过使用小鼠 PDGF 受体的心外膜特异性功能丧失等位基因来实现。该提案的具体目标是: 1)确定PDGF受体在心外膜初始发育中的作用机制; 2) 阐明冠状血管平滑肌细胞和心脏成纤维细胞对PDGFR2的需求; 3) 确定心脏内成纤维细胞的发育和功能是否需要 PDGFR1 信号传导。了解心外膜和心外膜衍生细胞中 PDGF 受体功能的机制将为了解控制心外膜细胞生物学的信号传导机制提供重要见解,并有可能揭示可用于控制心脏损伤后纤维化和直接血管生成的信号传导途径。公众健康相关性:心脏纤维化和冠状动脉功能受损是心脏病的两个主要特征,但很少有药物或疗法能够作用于导致这些问题的细胞。这项研究的目标是识别可以改变这些细胞类型的形成和功能的信号。操纵这些信号可以改善心脏损伤的结果。这些研究的成功将为推进修复受损心脏和减少纤维化的治疗提供信息。

项目成果

期刊论文数量(0)
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Michelle D Tallquist其他文献

Michelle D Tallquist的其他文献

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{{ truncateString('Michelle D Tallquist', 18)}}的其他基金

The role of lung lipofibroblasts in alveolar differentiation
肺脂肪成纤维细胞在肺泡分化中的作用
  • 批准号:
    10331843
  • 财政年份:
    2021
  • 资助金额:
    $ 39.25万
  • 项目类别:
Regulation of cardiac inflammation by fibroblasts
成纤维细胞调节心脏炎症
  • 批准号:
    9762629
  • 财政年份:
    2018
  • 资助金额:
    $ 39.25万
  • 项目类别:
Regulation of cardiac inflammation by fibroblasts
成纤维细胞调节心脏炎症
  • 批准号:
    10238764
  • 财政年份:
    2018
  • 资助金额:
    $ 39.25万
  • 项目类别:
Regulation of cardiac inflammation by fibroblasts
成纤维细胞调节心脏炎症
  • 批准号:
    9815100
  • 财政年份:
    2018
  • 资助金额:
    $ 39.25万
  • 项目类别:
PDGF Receptor Signaling in Mammalian Development
哺乳动物发育中的 PDGF 受体信号传导
  • 批准号:
    7655215
  • 财政年份:
    2009
  • 资助金额:
    $ 39.25万
  • 项目类别:
PDGF Receptor Signaling in Mammalian Development
哺乳动物发育中的 PDGF 受体信号传导
  • 批准号:
    8242728
  • 财政年份:
    2009
  • 资助金额:
    $ 39.25万
  • 项目类别:
PDGF Receptor Signaling in Mammalian Development
哺乳动物发育中的 PDGF 受体信号传导
  • 批准号:
    8775036
  • 财政年份:
    2009
  • 资助金额:
    $ 39.25万
  • 项目类别:
PDGF Receptor Signaling in Mammalian Development
哺乳动物发育中的 PDGF 受体信号传导
  • 批准号:
    8511775
  • 财政年份:
    2009
  • 资助金额:
    $ 39.25万
  • 项目类别:
PDGF Receptor Signaling in Mammalian Development
哺乳动物发育中的 PDGF 受体信号传导
  • 批准号:
    7787511
  • 财政年份:
    2009
  • 资助金额:
    $ 39.25万
  • 项目类别:
PDGF Receptor Signaling in Mammalian Development
哺乳动物发育中的 PDGF 受体信号传导
  • 批准号:
    7069095
  • 财政年份:
    2003
  • 资助金额:
    $ 39.25万
  • 项目类别:

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