MOLECULAR ANALYSIS OF ELASTIC FIBERS IN THE BLADDER

膀胱中弹性纤维的分子分析

• 批准号: 2414933
• 负责人: JOEL ROSENBLOOM
• 金额: $ 22.5万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-15 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2414933
• 关键词: RNA splicing; animal tissue; collagen; developmental genetics; elasticity; elastin; embryo /fetus cell /tissue; extracellular matrix; fibrillin; gene expression; histogenesis; human fetus tissue; immunocytochemistry; in situ hybridization; interleukin 1; messenger RNA; microfilaments; northern blottings; protein biosynthesis; smooth muscle; tissue /cell culture; tumor necrosis factor alpha; urinary bladder; urination; western blottings

The normal bladder has the ability to accommodate to large fluid volume changes without untoward pressure changes. Retention of this crucial function requires, among other variables, the maintenance of a complex extracellular matrix in both the mucosa and muscular detrusor layers. However, relatively little is known concerning the detailed molecular characteristics of this matrix either during development of the bladder or in disease situations. This proposal focuses on one of the major fibrous components of the bladder extracellular matrix, the elastic fiber, because of its central importance in normal function and because one of the cardinal features of a number of pathological conditions affecting the bladder is a loss of compliance and elastic recoil. The specific aims of the proposal are to: (1) relate the molecular composition and temporal sequence of expression of components of the elastic fiber to the elastic properties of the developing bladder, (2) analyze the synthesis of components of the elastic fiber by cultured bladder smooth muscle cells, fibroblasts and urothelial cells, (3) determine the spatial distribution of elastic fiber components in the developing bladder. In order to achieve these aims, this proposal will apply rapidly accumulating new information concerning the identification and characterization of the proteins composing the elastic fiber and utilize state of the art molecular biologic, biochemical, immunologic, and ultrastructural analytical techniques. The bladders and cultured cells of male and female human and bovine fetuses of representative developmental ages will be analyzed. The results of these studies will shed light on extracellular matrix structure/function relationships in the bladder and identify specific proteins which may be involved in loss of the important property of elasticity.

正常膀胱具有适应大量流体体积的能力 没有压力变化而变化。保留这个关键 功能除其他变量外需要维护复合物 粘膜和肌肉弯曲层中的细胞外基质。 但是，关于详细分子的相对较少 该矩阵在膀胱开发过程中的特征或 在疾病情况下。该提案重点是主要的纤维之一 膀胱外基质（弹性纤维）的成分，因为 它在正常功能中的重要性，因为 许多病理状况的基本特征影响 膀胱是失去依从性和弹性后坐力。具体目的 该提议是：（1）将分子组成和时间关联 弹性纤维成分表达的序列 发育膀胱的特性，（2）分析合成 通过培养的膀胱平滑肌细胞的弹性纤维成分， 成纤维细胞和尿路上皮细胞，（3）确定空间分布 发育中的膀胱中的弹性纤维成分。为了实现 这些目的，该建议将迅速累积新信息 关于蛋白质的识别和表征 组成弹性纤维并利用艺术分子的状态 生物学，生化，免疫和超微结构分析 技术。男性和女性人类的膀胱和培养细胞以及 将分析代表性发育年龄的牛胎儿。 这些研究的结果将阐明细胞外基质 膀胱中的结构/功能关系并确定特定 可能涉及丧失重要特性的蛋白质 弹性。