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Urine concentrating mechanisms examined by molecular biology based techniques

通过基于分子生物学的技术检查尿液浓缩机制

基本信息

批准号：
06404041
负责人：
MARUMO Fumiaki
金额：
$ 26.11万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

项目摘要

In this research, we intended to clarify three aspects of the mechanisms underlying kidney urinary concentrating ability.1) Cloning of transport proteins related to kidney urinary concentrating ability and examinationof their structure and function relationships. As new trasporters, we have cloned AQP3, AQP6, ClC-K2, ClC-3, and ClC-5. AQP3 is the basolateral type water channel of kidney collecting duct and it permeates small solutes such as glycerol. AQP6 also belongs to the same subfaily as AQP3, and it functional characters are similar to AQP3. ClC-5 has an unique character of strong outward rectification and its mRNA distributes in many tissues.2) Idnetification of the signaling mechanisms controlling urinary concentrating ability. We observed the upregulation of mRNA of AQP2 and AQP3 by dehydration. The mechanisms for this regulation was identifyed by isolation of genomic sequences of the 5'region of the both genes. We also identified that A-kinse plays critical roles in the regulation of AQP2. Similar studies are under way for ClC-K1 and ClC-K2.3) Application of basic research information ot clinical medicine. Research results obtained in this project have many implication to clinical field. Regulation of AQP2 was examined in many experimental models of water balance disorders. Urinary measurement of AQP2 has been shown to be of clinical importance in diagnosis of water balance disorders. Also immunohistochemical study using antibodies against AQPs differentiated the origin of renal carcinoma.

在这项研究中，我们打算阐明肾脏尿浓缩能力的三个方面的机制。1)肾尿浓缩能力相关转运蛋白的克隆及其结构与功能关系的研究。作为新的转运体，我们克隆了AQP3、AQP6、ClC-K2、ClC-3和ClC-5。AQP3为肾集管基底外侧型水道，可渗透甘油等小溶质。AQP6与AQP3同属一个亚科，其功能特征与AQP3相似。ClC-5具有向外强整流的独特特性，其mRNA分布在许多组织中。2)确定控制尿浓缩能力的信号机制。我们观察到脱水后AQP2和AQP3 mRNA表达上调。这种调控机制是通过分离两个基因的5'区基因组序列来确定的。我们还发现a -激酶在AQP2的调控中起关键作用。ClC-K1和ClC-K2.3)基础研究信息在临床医学中的应用。本课题的研究成果对临床具有重要意义。AQP2的调控在许多水平衡失调的实验模型中得到了检验。尿中AQP2的测定已被证明对诊断水平衡紊乱具有临床重要性。同时利用AQPs抗体进行免疫组化研究，鉴别肾癌的来源。