STRUCTURE, FUNCTION AND DEVELOPMENT OF THE JUXTAGLOMERULAR APPARATUS

近球装置的结构、功能和发展

• 批准号: 3876191
• 负责人: DALE ABRAHAMSON
• 金额: --
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3876191
• 关键词: apical membrane; chemical structure function; electrochemistry; growth /development; histochemistry /cytochemistry; immunochemistry; immunofluorescence technique; juxtaglomerular apparatus; organelles; renal glomerulus; renal tubular transport

The structural and functional interrelationships between the macula densa, extraglomerular mesangium, and other cells of the juxtaglomerular apparatus (JGA) are incompletely understood. In addition, few studies on the development of this area of the nephron have been undertaken. We intend to use a combination of physiological, morphological, and immunocytochemical techniques to describe, at a cellular level, the structure and function of the JGA in vivo and in vitro. First, using the isolated thick ascending limb with attached glomerulus, we will examine in vitro and in tissue fixed for electron microscopy structural rearrangements within intra- and extracellular compartments that might occur during changes in luminal osmolality. Second, the permeability properties of the extracellular matrix of the JGA will be tested in vitro with the addition of sized fluorphores and tracers for light and electron microscopy added to the bathing solution. Third, we intend to label in vivo the extracellular matrix of the developing JGA of newborn rats and rabbits to study its sequence of assembly and cellular origin. In addition, the appearance of renin- and angiotensin-containing cells will be determined immunocytochemically and correlated with the stage of glomerular development. Fourth, the acquisition of functional properties of the JGA will be determined by measuring plasma renin levels in developing animals and renin release from the isolated thick ascending limb with attached JGA preparation. Ultimately, these experiments in normal animals will be extended to genetic and experimental models of hypertension to determine whether JGA dysfunction and/or abnormal JGA development might be one of the relevant factors contributing to the development of hypertension.

结构和功能之间的相互关系 致密斑、肾小球外系膜和其他细胞 肾小球旁装​​置（JGA）尚未完全了解。 此外，关于该领域发展的研究还很少。 肾单位已进行。 我们打算使用一个组合 生理学、形态学和免疫细胞化学 在细胞水平上描述结构和 JGA 的体内和体外功能。 首先，使用隔离 厚的升肢与附着的肾小球，我们将检查 体外和组织内固定用于电子显微镜结构 细胞内和细胞外的重排 这可能发生在管腔渗透压变化期间。 第二， 细胞外基质的通透性 JGA 将通过添加一定尺寸的荧光团进行体外测试 以及添加到光学和电子显微镜的示踪剂 沐浴液。 第三，我们打算在体内标记 新生大鼠发育中的 JGA 的细胞外基质和 兔子研究其组装序列和细胞起源。 在 此外，含肾素和血管紧张素的出现 细胞将通过免疫细胞化学测定并相关 与肾小球发育阶段有关。 第四， 收购 JGA 的功能特性将是 通过测量发育中的血浆肾素水平来确定 动物和肾素从孤立的厚升肢中释放 附带 JGA 准备。 最终，这些实验 在正常动物中将扩展到遗传和实验 高血压模型以确定 JGA 是否功能障碍 和/或 JGA 发育异常可能是相关原因之一 导致高血压发生的因素。