CELLULAR REMODELING POST OBSTRUCTION OF UROGENITAL TRACT

泌尿生殖道梗阻后的细胞重塑

• 批准号: 6176616
• 负责人: WILLIAM DONALD STEERS
• 金额: $ 60.95万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6176616
• 关键词: male reproductive system; male reproductive system disorder; urinary tract; urinary tract obstruction

Acquired and congenital obstruction of the vas deferens, ureter and renal vasculature, lead to alterations in reproductive and kidney function. This renewal for an O'Brian urology Research Center is focused on the cellular and molecular mechanisms underlying neonatal or pre-pubertal obstruction of the testis, epididymidis, and kidney. Four projects by established senior investigators are proposed. Project 1 investigates the altered phenotype of renal tubular epithelial cells (RTE) after neonatal ureteral obstruction. Deranged cellular polarity, apoptosis and crosstalk between RTE and interstitial fibroblasts will be examined in a ureteral and single nephron obstruction models offering insight into pediatric hydronephrotic disorders. Project 2 investigates the regulatory mechanisms and genomic events leading to the development of obstructed renal vasculature, especially with regard to the role of angiotensin in preserving normal renal vascular morphology. Phenotypic changes, vascular remodeling, and the lineage of cells participating in vessel growth in angiotensin deficient mice will be investigated. Project 3 studies the effect of vasal obstruction on epithelial function both proximal to (epididymis) and distal to (prostate) the site of obstruction. Cellular biochemistry and synthetic events will be studies. Reversibility of changes in protein synthesis and luminal secretion following relief of obstruction will be studied in both epididymis and prostate. These data will provide insight into persistent infertility after vasovasotomy and determine if vasectomy alters prostate growth or function. Project 4 explores the effects of pre-pubertal and adult obstruction on seminiferous epithelium, induction of antisperm antibodies, and characterization of sperm autoantigens. These findings may identify new and important sperm antigens involved in reproductive tract alterations (fertility). Investigators in this P50 share common themes, mechanisms and methods of investigation. These projects represent a refinement and focusing of efforts, building on strengths in reproductive biology and pediatric nephrology at the University of Virginia.

获得性和先天性输精管、输尿管和输精管梗阻 肾血管系统，导致生殖和肾脏的改变 功能。 奥布莱恩泌尿学研究中心的更新是 专注于潜在的细胞和分子机制 新生儿或青春期前的睾丸、附睾和睾丸梗阻 肾。已设立的高级研究人员的四个项目是 建议的。 项目 1 研究肾表型的改变 新生儿输尿管梗阻后的肾小管上皮细胞（RTE）。 细胞极性紊乱、细胞凋亡和 RTE 之间的串扰 间质成纤维细胞将在输尿管和单个 肾单位阻塞模型可深入了解儿科 肾积水疾病。 项目2 调查监管 导致发展的机制和基因组事件 肾血管系统阻塞，特别是在肾血管系统的作用方面 血管紧张素可维持正常的肾血管形态。 表型变化、血管重塑和细胞谱系 参与血管紧张素缺乏小鼠的血管生长 调查了。 项目 3 研究血管阻塞的影响 近端（附睾）和远端的上皮功能 （前列腺）阻塞部位。细胞生物化学和 综合事件将被研究。 蛋白质变化的可逆性 阻塞缓解后的合成和管腔分泌将 在附睾和前列腺中进行研究。 这些数据将提供 深入了解输精管结扎术后持续不孕并确定是否 输精管切除术会改变前列腺的生长或功能。项目 4 探索 青春期前和成人梗阻对生精的影响 上皮、抗精子抗体的诱导和表征 精子自身抗原。 这些发现可能会发现新的和 参与生殖道改变的重要精子抗原 （生育能力）。 P50 中的调查人员有共同的主题， 调查机制和方法。 这些项目代表 精益求精、集中力量，发挥优势 生殖生物学和儿科肾脏病学大学 弗吉尼亚。