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Molecular approaches to the pathogenesis of glomerulanephritis by vasoactive substances

血管活性物质对肾小球肾炎发病机制的分子研究

基本信息

批准号：
05837007
负责人：
TERADA Yoshio
金额：
$ 1.09万
依托单位：
Tokyo Medical & Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
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

项目摘要

Renal nephron segments were heterogeneous, and receptors for endothelin (ET)-1, ET-3, Angiotensin II (AT II), EGF,and IGF-1 distribute differently along the nephron segments. We have revealed that the PCR localizatoin of two types (V2, V1) of vasopressin receptor, and angiotensin II receptor. We also reported that localization of mRNA and protein of ET-3 along the nephron segments. Recently, growth factors and vasoactive substances are reported to stimulate mitogen-activated protein kinase (MAP-K). In this study, we showed that mRNA of MEK-K,Raf-1-K,MAPK-K,MAP-Ks(p42 and p44), and S6-K was expressed in nephron segments using RT-PCR technique. We showed that MAP-K cascades are expressed in every nephron segment. ET-1, ET-3, AT II,EGF,and IGF-I stimulate MAP-K cascades heterogeneously along the nephron segment. We concluded that MAP-K cascades play an important role in the regulation of renal function. We also reported that the presence of C-type natriuretic factor and its receptor (GC-B) along the nephron. The CNP system may play an important roles in modulatiing the salt and body fluid homeostasis and blood pressure. We also analyzed the expression of PDGF and PDGF-receptor expression in the glomeruli of IgA nephropathy patients. Thus, we investigated the new approaches to the pathogenesis of glomerulonephritis and renal functions.

肾单位各节段的内皮素（ET）-1、ET-3、血管紧张素II（AT II）、EGF和IGF-1受体分布沿着肾单位各节段不同。我们发现，两种类型的加压素受体（V2，V1）和血管紧张素II受体的PCR定位。我们还报道了ET-3 mRNA和蛋白在肾单位各节段的沿着分布。最近，生长因子和血管活性物质被报道刺激丝裂原活化蛋白激酶（MAP-K）。本研究采用RT-PCR技术，发现MEK-K、Raf-1-K、MAPK-K、MAP-Ks（p42和p44）和S6-K的mRNA在肾单位节段中表达。我们发现MAP-K级联在每个肾单位节段中表达。ET-1、ET-3、AT II、EGF和IGF-I沿着肾单位节段不均匀地刺激MAP-K级联。我们的结论是，MAP-K级联在肾功能的调节中发挥重要作用。我们还报道了C型利钠因子及其受体（GC-B）沿着肾单位的存在。CNP系统可能在调节盐和体液平衡以及血压方面发挥重要作用。我们还分析了伊加肾病患者肾小球中PDGF和PDGF受体的表达。因此，我们探讨了肾小球肾炎的发病机制和肾功能的新途径。