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Molecular Biology of the Kidney-Molecular Analysis of Structure and Function Relationship

肾脏的分子生物学-结构与功能关系的分子分析

基本信息

批准号：
05304037
负责人：
MARUMO Fumiaki
金额：
$ 1.54万
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 Co-operative Research (A)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05304037/
关键词：
Molecular biology Nephrology Cloning Glomerulus Nephron Transporter Basement Membrane Hormone cloning Transporter Basement membrane

项目摘要

We have investigated three major aspects of the kidney.1) Glomerular matrix and glomerular function. We found a mutations of alpha 5 chain of typelV collagen gene in patients with Alport syndrome. This result confirm the significance of basement membrane collagen in glomerular function. We also showed that glycosilated substances stimulates the transcription of extracellular matrix genes. This stimulation is important for the sclorotic changes of glomerulus frequently observed in diabetes meditus.2) Regulation of bioactive substances and their receptors. We showed the presence of TGFb mRNA in glomerulus, all nephron segments, small renal arteiries. On the other hand, mRNA of LTBP,which is important for activation of TGFb, is present only in glomerulus and small renal arteiries. We also developed a new acurate method for quantification of RTPCR which is critically needed for small piece of tissues such as dissected nephron segments. Usin this method we showed the nephron localization of mRNA of PGE2 receptor.3) Cloning and characterization of kidney trnasport proteins. We cloned a kidney collecting duct water channel named AQP3, which is localized at the basolateral membrane. We showed many regulational mechanisms of AQP2 at trnascriptional, protein, and cellular levels. We anso cloned a rat dipeptide transporter in the kidney, and found that this transporter works as a rout for cepharosporin antibiotics.

我们研究了肾脏的三个主要方面。1）肾小球基质和肾小球功能。我们在Alport综合征患者中发现了IV型胶原蛋白基因α5链的突变。该结果证实了基底膜胶原在肾小球功能中的重要性。我们还表明糖基化物质刺激细胞外基质基因的转录。这种刺激对于糖尿病中期经常观察到的肾小球硬化变化很重要。2）生物活性物质及其受体的调节。我们发现肾小球、所有肾单位节段、小肾动脉中存在 TGFb mRNA。另一方面，LTBP 的 mRNA 对 TGFb 的激活很重要，仅存在于肾小球和小肾动脉中。我们还开发了一种新的准确的 RTPCR 定量方法，这对于小块组织（例如解剖的肾单位片段）至关重要。利用该方法我们展示了PGE2受体mRNA的肾单位定位。3)肾转运蛋白的克隆和表征。我们克隆了一个名为 AQP3 的肾集合管水通道，它位于基底外侧膜。我们在转录、蛋白质和细胞水平上展示了 AQP2 的许多调节机制。我们还克隆了大鼠肾脏中的二肽转运蛋白，并发现该转运蛋白可作为头孢菌素抗生素的路径。