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.

正常的膀胱具有容纳大量液体的能力。 变化而不会有不利的压力变化。保留这一至关重要的 在其他变量中，函数需要维护复杂的 粘膜和肌肉逼尿肌层中的细胞外基质。 然而，关于详细的分子相对知之甚少。 该基质在膀胱或膀胱发育过程中的特征 在疾病的情况下。这项建议主要集中在一种主要的纤维 膀胱细胞外基质的成分，弹性纤维，因为 它在正常功能中的核心重要性，因为 一些影响心脏的病理情况的基本特征 膀胱是一种失去顺应性和弹性的后座力。的具体目标 建议是：(1)将分子组成和时间联系起来 弹性纤维的各组分对弹性的表达顺序 发育中膀胱的性质，(2)分析合成 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)决定空间分布 在发育中的膀胱中的弹性纤维成分。为了实现 这些目的，这项建议将应用迅速积累新的信息 关于蛋白质的鉴定和特性 弹性纤维的合成及其分子应用现状 生物、生化、免疫学和超微结构分析 技巧。男性和女性的膀胱和培养细胞 对具有代表性发育年龄的牛胎儿进行分析。 这些研究的结果将有助于了解细胞外基质。 膀胱中的结构/功能关系并识别特定的 可能与失去重要性质有关的蛋白质 弹性。