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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05837007/
• 关键词: gene expression; PCR; cell proliferation; glomerulonephritis; PDGF; CNP; MAP kinase; signal transduction; エンドセリン; 抗利尿ホルモン

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.

肾肾单元段具有异质性，内皮素(ET)-1、ET-3、血管紧张素II （AT II）、EGF和IGF-1受体沿肾单元段分布不同。我们发现了血管加压素受体和血管紧张素II受体的两种类型（V2, V1）的PCR定位。我们还报道了ET-3 mRNA和蛋白沿肾元段的定位。近年来，生长因子和血管活性物质被报道可以刺激有丝分裂原活化蛋白激酶（MAP-K）。在本研究中，我们利用RT-PCR技术发现MEK-K、Raf-1-K、MAPK-K、map - k （p42和p44）和S6-K的mRNA在肾细胞片段中表达。我们发现MAP-K级联在每个肾元段表达。ET-1、ET-3、AT II、EGF和IGF-I刺激MAP-K沿着肾元段不均匀级联。我们认为MAP-K级联在肾脏功能的调节中起重要作用。我们也报道了沿肾元存在c型利钠因子及其受体（GC-B）。CNP系统可能在调节盐、体液稳态和血压中起重要作用。我们还分析了IgA肾病患者肾小球中PDGF和PDGF受体的表达。因此，我们探索肾小球肾炎的发病机制和肾功能的新途径。

项目成果

Y.Terada, K.Tomita, H.Nonoguchi, F.Marumo: "PCR localization of angiotensin II receptor and angiotensnogen mRNAs in rat kidney." Kidney International. 43. 1251-125

Y.Terada、K.Tomita、H.Nonoguchi、F.Marumo：“大鼠肾脏中血管紧张素 II 受体和血管紧张素原 mRNA 的 PCR 定位。”

Masakazu Otuka: "Localization of cyclophilm A and cyclophilmC mRNA in murine Kidney using RT-PCR" Kidney International. 45. 1340-1345 (1994)

Masakazu Otuka：“使用 RT-PCR 定位小鼠肾脏中的 cyclophilm A 和 cyclophilmC mRNA”肾脏国际。

Y.Terada, K.Tomita, H.Nonoguchi, T.Yang, F.Marumo: "Expression of endothelin-along rat nephron segments using PCR." Kidney International. 344. 1273-1280 (1993)

Y.Terada、K.Tomita、H.Nonoguchi、T.Yang、F.Marumo：“使用 PCR 表达内皮素沿大鼠肾单位片段。”

Yoshio Terada: "Sequential Activation of raf-1 kinase,MAP-kinase,Kinase,MAP kinase and s6 kinase by hyperosmolality in vevol cell" Journal of Biological Chemistory. 269. 31296-31301 (1994)

Yoshio Terada：“vevol 细胞中高渗性依次激活 raf-1 激酶、MAP 激酶、激酶、MAP 激酶和 s6 激酶”《生物化学杂志》。

Kimio Tomita et al: "Effects of ET-1 on water and chloride transport in cortical collecting clucts of the rat" American Journal of Physiology. 264. F690-F696 (1993)

Kimio Tomita 等人：“ET-1 对大鼠皮质集合管中水和氯离子运输的影响”美国生理学杂志。