Alveolar Basement Membrane/Cell Interactions in the Lung
肺中肺泡基底膜/细胞的相互作用
基本信息
- 批准号:6830707
- 负责人:
- 金额:$ 29.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1996
- 资助国家:美国
- 起止时间:1996-09-01 至 2007-11-30
- 项目状态:已结题
- 来源:
- 关键词:basement membranebinding proteinscell cell interactioncell growth regulationelectron microscopyenzyme linked immunosorbent assayextracellular matrixfibroblast growth factorfibroblastsgene expressiongenetically modified animalsgrowth factor receptorshistopathologyimmunocytochemistrylaboratory ratnorthern blottingsnucleic acid chemical synthesispolymerase chain reactionreceptor bindingrespiratory epitheliumsulfationsyndecantissue /cell culturetransfectionwestern blottings
项目摘要
DESCRIPTION (provided by applicant): The epithelium of the alveolar region of the lung is susceptible to injury, such as that induced by air-borne toxicants or oxidant stress. Interruption/delay of the replacement of these cells following injury results in faulty repair and irreversibly impaired function in the alveolus. In this proposal, we will show that there exists a critical, dynamic relationship between lung epithelial cells and fibroblasts that dictate their responsiveness to and expression of sulfated extracellular matrices (SECMs) and growth factors. This constitutes a dynamic barrier, modified by the cells themselves, that defines their selective division of labor, maximizes their common efficiency, and is reflected in specific counter-regulation of expression of these modulatory factors. The hypothesis to be addressed is: The sulfated extracellular matrix between alveolar epithelium and underlying fibroblasts selectively down-regulates generation and activity of key regulatory factors: FGF-1, -2, and -7, and their adaptor molecules (FGF-receptors, FGF-binding protein, and specific sulfated ECMs). These processes constitute critical paracrine and juxtacrine mechanisms for regulating cell numbers, cell functions, and cellular architectural arrangement under normal, hyperplastic, and disease states in the alveolus. Isolated AT2 cells will be co-cultured with fibroblasts and the intervening sulfated ECM environment modified by either exogenous addition or stimulated overproduction (enhancement) or selective inhibition/modification of gene/protein expression (reduction). To define the mechanisms that control critical epithelial cell-fibroblast interactions, cellular responses to over expression of key regulatory growth factors and inhibited translation of growth factor response adapters will be measured by DNA synthesis, relevant signaling events, and expression of selected gene/protein products. Whole animal studies using adenovector-mediated gene transfer will determine if over expression of FGF-BP or syndecan-1 improves or alters injury/repair outcomes in an in vivo model of pulmonary fibrosis. Results of these studies are expected to provide essential information needed to better understand basic cell-cell, celI-ECM relationships in homeostasis, as well as the mechanisms that steer the pathogenesis of fibrogenic change in the lung because of injury and/or disease.
描述(由申请方提供):肺肺泡区域的上皮细胞易受损伤,例如由空气传播的毒物或氧化剂应激诱导的损伤。 损伤后这些细胞替换的中断/延迟导致肺泡中的错误修复和不可逆的功能受损。 在这个建议中,我们将表明,肺上皮细胞和成纤维细胞之间存在着一个关键的,动态的关系,决定他们的反应和表达的硫酸化细胞外基质(SECM)和生长因子。 这构成了一个动态的屏障,由细胞本身进行修改,定义了它们的选择性分工,最大限度地提高了它们的共同效率,并反映在这些调节因子表达的特定反调节中。 要解决的假设是:肺泡上皮细胞和下层成纤维细胞之间的硫酸化细胞外基质选择性下调关键调节因子的产生和活性:FGF-1,-2和-7,及其衔接分子(FGF受体,FGF结合蛋白和特定的硫酸化ECM)。 这些过程构成了调节肺泡中正常、增生和疾病状态下细胞数量、细胞功能和细胞结构排列的关键旁分泌和旁分泌机制。 将分离的AT 2细胞与成纤维细胞共培养,并通过外源性添加或刺激的过度生产(增强)或基因/蛋白质表达的选择性抑制/修饰(减少)来修饰干预的硫酸化ECM环境。 为了确定控制关键上皮细胞-成纤维细胞相互作用的机制,将通过DNA合成、相关信号传导事件和选定基因/蛋白质产物的表达来测量对关键调节生长因子过度表达和生长因子应答衔接子翻译抑制的细胞应答。 使用腺病毒载体介导的基因转移的整个动物研究将确定是否FGF-BP或syndecan-1的过表达改善或改变肺纤维化的体内模型中的损伤/修复结果。 这些研究的结果有望提供必要的信息,以更好地了解基本的细胞-细胞,细胞-ECM的动态平衡的关系,以及机制,引导肺纤维化的变化,因为损伤和/或疾病的发病机制。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Philip L. Sannes其他文献
Philip L. Sannes的其他文献
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{{ truncateString('Philip L. Sannes', 18)}}的其他基金
Differentiation of Alveolar Epithelium in Pulmonary Fibrosis
肺纤维化中肺泡上皮的分化
- 批准号:
7708480 - 财政年份:2009
- 资助金额:
$ 29.2万 - 项目类别:
Differentiation of Alveolar Epithelium in Pulmonary Fibrosis
肺纤维化中肺泡上皮的分化
- 批准号:
7837603 - 财政年份:2009
- 资助金额:
$ 29.2万 - 项目类别:
Alveolar Basement Membrane/Cell Interactions in the Lung
肺中肺泡基底膜/细胞的相互作用
- 批准号:
6728168 - 财政年份:1996
- 资助金额:
$ 29.2万 - 项目类别:
Alveolar Basement Membrane/Cell Interactions in the Lung
肺中肺泡基底膜/细胞的相互作用
- 批准号:
8449159 - 财政年份:1996
- 资助金额:
$ 29.2万 - 项目类别:
Alveolar Basement Membrane/Cell Interactions in the Lung
肺中肺泡基底膜/细胞的相互作用
- 批准号:
8235914 - 财政年份:1996
- 资助金额:
$ 29.2万 - 项目类别:
Alveolar Basement Membrane/Cell Interactions in the Lung
肺中肺泡基底膜/细胞的相互作用
- 批准号:
6969923 - 财政年份:1996
- 资助金额:
$ 29.2万 - 项目类别:
Alveolar Basement Membrane/Cell Interactions in the Lung
肺中肺泡基底膜/细胞的相互作用
- 批准号:
7625297 - 财政年份:1996
- 资助金额:
$ 29.2万 - 项目类别:
Alveolar Basement Membrane/Cell Interactions in the Lung
肺中肺泡基底膜/细胞的相互作用
- 批准号:
7146014 - 财政年份:1996
- 资助金额:
$ 29.2万 - 项目类别:
Alveolar Basement Membrane/Cell Interactions in the Lung
肺中肺泡基底膜/细胞的相互作用
- 批准号:
8048112 - 财政年份:1996
- 资助金额:
$ 29.2万 - 项目类别:
Alveolar Basement Membrane/Cell Interactions in the Lung
肺中肺泡基底膜/细胞的相互作用
- 批准号:
7799765 - 财政年份:1996
- 资助金额:
$ 29.2万 - 项目类别:
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