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.

正常膀胱具有容纳大量液体的能力 变化时不会产生不良的压力变化。保留这一关键 除其他变量外，函数还需要维护一个复杂的 粘膜层和逼尿肌层中的细胞外基质。 然而，人们对详细的分子机制知之甚少。 该基质的特征在膀胱发育过程中或 在疾病情况下。该提案重点关注主要纤维之一 膀胱细胞外基质的成分，弹性纤维，因为 其在正常功能中的核心重要性，并且因为其中之一 一些影响疾病的病理状况的主要特征 膀胱失去顺应性和弹性反冲力。具体目标 建议是：（1）将分子组成和时间联系起来 弹性纤维各成分对弹性体的表达顺序 发育中膀胱的特性，（2）分析合成 由培养的膀胱平滑肌细胞组成的弹性纤维成分， 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。为了达到 这些目标，该提案将迅速积累新信息 关于蛋白质的鉴定和表征 组成弹性纤维并利用最先进的分子 生物学、生化、免疫学和超微结构分析 技术。男性和女性人类的膀胱和培养细胞 将分析具有代表性发育年龄的牛胎儿。 这些研究结果将揭示细胞外基质 膀胱的结构/功能关系并确定特定的 可能与重要特性丧失有关的蛋白质 弹性。