Identification of Novel Proteins Secreted by the Kidney

描述(申请人提供)：血液透析疗法是一种挽救慢性终末期肾病或急性肾功能衰竭患者生命的方法。然而，与这种疗法相关的发病率和死亡率高得令人不快，而且许多患者的生活质量很差。这些不太理想的结果的原因还不完全清楚。由于该手术使用的是体外“人工肾”来清除血液中多余的水分和可溶性废物，它不能复制自然器官的重要吸收、代谢、内分泌和免疫功能。因此，极有可能是肾功能的不完全替代导致透析患者预后不佳。 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肾素和促红细胞生成素的分泌。肾脏分泌的以前未知的蛋白质/激素的特征不仅将提供对肾脏生理的更完整的了解，而且还可能显著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，这项提议旨在利用人类功能基因组数据库识别肾脏分泌的新蛋白质，并结合一种创新的基因表达方法，这种方法可以快速并行分析许多基因。在这个提案中，我们解决了三个问题：1)哪些新的候选基因可能编码分泌蛋白？2)候选基因在肾脏中特异表达还是高度表达？3)这些候选基因是否真的编码分泌蛋白？

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?