Development and plasticity of ICC

ICC的发展与可塑性

基本信息

  • 批准号:
    6801332
  • 负责人:
  • 金额:
    $ 17.39万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2004
  • 资助国家:
    美国
  • 起止时间:
    2004-05-01 至 2009-04-30
  • 项目状态:
    已结题

项目摘要

Tissues isolated from different regions of the gastrointestinal tract, display spontaneous electrical and mechanical activity. When contractions and membrane potential are recorded simultaneously each contraction is triggered by a long lasting wave of depolarization that have been termed slow waves. The origin and basis for the generation of slow wave activity has been debated for many years but it is now widely accepted that these pacemaker potentials arise from a separate group of cells, known as interstitial cells of Cajal (ICC). The mechanical activity of most smooth muscle cells is also modified by autonomic or enteric nerves. Previously it was thought that neurotransmission in smooth muscles occurred by simple diffusion. However, it appears that nerve terminals, rather than communicating directly with smooth muscle cells, form close synaptic relationships with ICC in several regions of the GI tract. These contacts are necessary for coordinated motor neurotransmission in GI muscles. Motility disorders have traditionally been characterized as either myopathic or neuropathic in origin, although a large majority of patients that suffer from these disorders do not display obvious histopathological changes in either enteric nerves or smooth muscle cells in biopsies. The discovery that ICC express the receptor tyrosine kinase, Kit has provided pathologists and gastroenterologists with a means to access the changes in ICC that occur in patients with both congenital or acquired motility disorders. Several recent clinical studies have indicated that a variety of unrelated motility disorders of the GI tract may be linked to improper development of lCC or loss of ICC in mature tissues. The underlying causes for compromised Kit signaling and loss of ICC in patients have led to the development of several animal models where changes in ICC networks can be systematically investigated. Using a combination of morphological and physiological approaches together with organotypic cultures and murine animal models that mimic human disorders, the importance of Kit signaling for the development and maintenance of lCC networks will be investigated in this proposal. Specific questions will examine: (A) the importance of the Kit signaling pathway for ICC development prior to and after birth (ii) the phenotypic plasticity of ICC during and after development and (iii) how ICC networks are affected under pathophysiological conditions that alter GI motility and are ICC capable of repopulating tissues after removal of pathophysiological insults. Information obtained from this proposal may provide insight into the mechanisms leading to the loss of these cells and associated motility disorders in humans.
从胃肠道的不同区域分离的组织显示自发的电和机械活动。当同时记录收缩和膜电位时,每一次收缩都是由被称为慢波的持久去极化波触发的。慢波活动产生的起源和基础已经争论了很多年,但现在广泛接受的是,这些起搏电位来自一组单独的细胞,称为Cajal间质细胞(ICC)。大多数平滑肌细胞的机械活动也被自主神经或肠神经改变。以前认为平滑肌中的神经传递通过简单扩散发生。然而,似乎神经末梢,而不是直接与平滑肌细胞沟通,在胃肠道的几个区域与ICC形成密切的突触关系。这些接触对于GI肌肉中的协调运动神经传递是必要的。运动障碍传统上被表征为起源于肌病或神经病,尽管患有这些疾病的绝大多数患者在活检中在肠神经或平滑肌细胞中不显示明显的组织病理学变化。ICC表达受体酪氨酸激酶的发现,Kit为病理学家和胃肠病学家提供了一种方法来访问先天性或获得性运动障碍患者中发生的ICC变化。最近的几项临床研究表明,各种不相关的胃肠道动力障碍可能与成熟组织中的ICC或ICC丢失的不适当发展有关。Kit信号传导受损和患者ICC丢失的根本原因导致了几种动物模型的发展,其中可以系统地研究ICC网络的变化。使用形态学和生理学方法的组合,连同器官型培养物和小鼠动物模型,模仿人类疾病,试剂盒信号的发展和维护的LCC网络的重要性将在本提案中进行调查。具体问题将审查:(A)Kit信号传导途径对出生前和出生后ICC发育的重要性,(ii)发育期间和发育后ICC的表型可塑性,以及(iii)ICC网络在改变GI运动性的病理生理条件下如何受到影响,并且ICC在去除病理生理损伤后能够重新填充组织。从这一建议获得的信息可能会提供深入了解的机制,导致这些细胞的损失和相关的运动障碍在人类。

项目成果

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Sean M Ward其他文献

Sean M Ward的其他文献

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{{ truncateString('Sean M Ward', 18)}}的其他基金

CORE C: PROTEIN EXPRESSION AND CELL MORPHOLOGY
核心 C:蛋白质表达和细胞形态
  • 批准号:
    8360523
  • 财政年份:
    2011
  • 资助金额:
    $ 17.39万
  • 项目类别:
CORE C: PROTEIN EXPRESSION AND CELL MORPHOLOGY
核心 C:蛋白质表达和细胞形态
  • 批准号:
    8168465
  • 财政年份:
    2010
  • 资助金额:
    $ 17.39万
  • 项目类别:
Mechanisms underlying regional differences in gastric compliance in the stomach.
胃顺应性区域差异的机制。
  • 批准号:
    7901981
  • 财政年份:
    2009
  • 资助金额:
    $ 17.39万
  • 项目类别:
Development and plasticity of Interstitial Cells of Cajal
卡哈尔间质细胞的发育和可塑性
  • 批准号:
    7413387
  • 财政年份:
    2007
  • 资助金额:
    $ 17.39万
  • 项目类别:
Development and plasticity of ICC
ICC的发展与可塑性
  • 批准号:
    7235349
  • 财政年份:
    2006
  • 资助金额:
    $ 17.39万
  • 项目类别:
Zeiss LSM 510 Laser Scanning Confocal Microscope
蔡司 LSM 510 激光扫描共焦显微镜
  • 批准号:
    6440771
  • 财政年份:
    2002
  • 资助金额:
    $ 17.39万
  • 项目类别:
Mechanisms underlying regional differences in gastric compliance in the stomach
胃顺应性区域差异的机制
  • 批准号:
    7647963
  • 财政年份:
    2000
  • 资助金额:
    $ 17.39万
  • 项目类别:
Mechanisms underlying regional differences in gastric compliance in the stomach.
胃顺应性区域差异的机制。
  • 批准号:
    7884627
  • 财政年份:
    2000
  • 资助金额:
    $ 17.39万
  • 项目类别:
INTERSTITIAL CELL OF CAJAL IN VAGAL AFFERENT SENSITIVITY
CAJAL间质细胞对迷走神经传入敏感性的影响
  • 批准号:
    6381743
  • 财政年份:
    2000
  • 资助金额:
    $ 17.39万
  • 项目类别:
INTERSTITIAL CELL OF CAJAL IN VAGAL AFFERENT SENSITIVITY
CAJAL间质细胞对迷走神经传入敏感性的影响
  • 批准号:
    6768684
  • 财政年份:
    2000
  • 资助金额:
    $ 17.39万
  • 项目类别:

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