CELLULAR REMODELING POST OBSTRUCTION OF UROGENITAL TRACT

获得性和先天性输精管、输尿管和 肾血管系统，导致生殖和肾脏 功能 O'Brian泌尿学研究中心的更新是 专注于细胞和分子机制， 新生儿或青春期前睾丸、附睾梗阻，以及 肾常设高级调查员的四个项目是 提出了 项目1研究肾细胞癌的表型改变， 新生儿输尿管梗阻后肾小管上皮细胞（RTE）。 细胞极性紊乱、凋亡和RTE之间的串扰 和间质成纤维细胞将在输尿管和单个 肾单位阻塞模型提供了对儿科的深入了解 肾积水疾病 项目2调查监管 机制和基因组事件导致的发展 肾血管阻塞，特别是在 血管紧张素维持正常肾血管形态。 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， 研究了 项目3研究血管阻塞对 上皮功能近端（附睾）和远端 （前列腺）阻塞的部位。细胞生物化学和 将研究合成事件。 蛋白质变化的可逆性 梗阻缓解后的合成和腔分泌将 在附睾和前列腺中进行研究。 这些数据将提供 深入了解血管切开术后持续性不孕，并确定 输精管切除术改变前列腺的生长或功能。项目4探索 青春期前和成年期梗阻对生精的影响 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 与生殖道改变有关的重要精子抗原 （生育率）。 P50的研究人员有着共同的主题， 调查的机制和方法。 这些项目代表了 完善和集中努力，利用 生殖生物学和儿科肾病学 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.