Identification of Novel Proteins Secreted by the Kidney

描述（由申请方提供）：血液透析治疗是慢性终末期肾病或急性肾衰竭患者的救命手术。然而，与该疗法相关的发病率和死亡率不期望地高，并且许多患者遭受较差的生活质量。这些不太理想的结果的原因还不完全清楚。由于该手术使用体外“人工肾”来去除血液中多余的水和可溶性废物，因此无法复制天然器官的重要吸收，代谢，内分泌和免疫功能。因此，很有可能是肾功能的不完全替代导致了透析患者的不良预后。 促红细胞生成素的发现强调了了解肾脏内分泌功能的重要性。有证据表明，肾脏的内分泌功能不仅限于分泌肾素和促红细胞生成素。对肾脏分泌的以前未知的蛋白质/激素的表征不仅可以更全面地了解肾脏生理学，而且还可以显着改善我们治疗终末期肾病患者的方式。作为这些努力的第一步，该提案旨在使用人类功能基因组学数据库识别肾脏分泌的新型蛋白质，再加上基因表达的创新方法，该方法允许并行快速分析许多基因。在这个建议中，我们解决了三个问题：1）什么是新的候选基因可能编码分泌蛋白？2)候选基因是否在肾脏中特异或高度表达？3)这些候选基因真的编码分泌蛋白吗？

DESCRIPTION (provided by applicant): Hemodialysis therapy is a life saving procedure for patients with either chronic end-stage renal disease or acute renal failure. However, the morbidity and mortality associated with this therapy are undesirably high, and many patients suffer from a poor quality of life. The causes for these less than ideal results are not entirely clear. Since the procedure uses an extracorporeal "artificial kidney" to remove excess water and soluble wastes from the blood, it can't replicate the important absorptive, metabolic, endocrine, and immunological functions of the natural organ. Therefore, a very strong possibility is that the incomplete replacement of kidney functions contributes to the dismal prognosis of patients on dialysis. The importance of understanding the kidney's endocrine function is underscored by the discovery of erythropoietin. There is evidence to suggest that the kidney's endocrine function is not limited to the secretion of renin and erythropoietin. The characterization of previously unknown proteins/hormones that are secreted by the kidney will not only provide a more complete understanding of renal physiology but may also significantly improve the way we treat patients with end-stage renal disease. As a first step toward these endeavors, this proposal is aimed at identifying novel proteins that are secreted by the kidney using a human functional genomics database, coupled with an innovative approach for gene expression, which allows rapid analysis of many genes in parallel. In this proposal, we address three issues: 1) What are the novel candidate genes potentially encoding secreted proteins? 2) Are the candidate genes specifically or highly expressed in the kidney? 3) Do these candidate genes indeed encode secreted proteins?