CELLULAR REMODELING POST OBSTRUCTION OF UROGENITAL TRACT

后天性和先天性输精管、输尿管和输尿管梗阻 肾血管系统，导致生殖和肾脏的改变 功能。奥布赖恩泌尿外科研究中心的续签是 重点放在细胞和分子机制上 新生儿或青春期前的睾丸、附睾部和 肾脏。由资深调查人员开展的四个项目是 建议。项目1研究肾脏表型的改变。 新生儿输尿管梗阻后的肾小管上皮细胞。 RTE之间的细胞极性错乱、细胞凋亡和串扰 间质成纤维细胞将在输尿管和单个输尿管中进行检查 肾单位梗阻模型提供对儿科的洞察 肾积水疾病。项目2调查监管机构 机制和基因组事件导致的发展 肾血管闭塞，尤其是与血管紧张素转换酶 血管紧张素在维持正常肾血管形态中的作用。 表型改变、血管重塑和细胞谱系 参与血管紧张素缺陷小鼠血管生长的将是 调查过了。项目3研究血管阻塞对心脏功能的影响。 附睾部近端和远端的上皮功能 (前列腺)阻塞的部位。细胞生物化学和 将对合成事件进行研究。蛋白质变化的可逆性 梗阻解除后的合成和腔内分泌 在附睾部和前列腺部都有研究。这些数据将提供 了解输精管切断术后持续性不孕症的情况并确定 输精管结扎术会改变前列腺的生长或功能。项目4探索了 青春期前和成年期梗阻对生精功能的影响 上皮细胞、抗精子抗体的诱导和特征 精子自身抗原。这些发现可能会发现新的和 与生殖道改变有关的重要精子抗原 (生育力)。这位P50的调查人员有共同的主题， 调查机制和调查方法。这些项目代表了 努力的精细化和重点，建立在 加州大学生殖生物学和儿科肾脏学 弗吉尼亚。

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.