Molecular Cell Biological Analysis on Renal Structure and Function

肾脏结构和功能的分子细胞生物学分析

• 批准号: 05404041
• 负责人: KUROKAWA Kiyoshi
• 金额: $ 24.32万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05404041/
• 关键词: mesangial cells; hypertension; insulin like growth factor-I (IGF-I); chloride; Ca signal; tubular function; prostaglandin; 糸球体機能; クロライド; インスリン様成長因子(IGF-I); 尿細管糸状体フィードバック; 副甲状腺関連ペプチド(PTHrP); ネフロン; 糸球体メサンギウム細胞; クロライドチャネル; Na-H輸送体; アンチセンス; R

The findings of the present research project include ; 1) in contrast to mesangial cells from normotensive rat, enhanced prostaglandin production and attenuation of Ca signal and contraction when extracellular Cl concentration was decreased were absent in mesangial cells of spontaneously hypertensive rat (SHR) and Dahl salt sensitive hypertensive rat (DS) ; 2) normal mesangial cell Ca signal and contraction was attenuated by insulin like growth factor (IGF)-I receptor activation ; 3) modulation of mesangial cell Ca signal and contraction by IGF-I was absent in SHR mesangial cells but present in DS mesangial cells ; 4) IGF-I infusion had no effect on GFR in SHR while it increased GFR in normotensive control rat ; 5) Na/H exchanger-I was present only on the basolateral side of LLCPK-1 cells ; 6) analysis of beta1 receptor mRNA expression revealed its expression in distal tubule ; and 7) Cl conductance was present on the basolateral side of rabbit proximal tubule.Furthermore, we advanced our hypothesis that disturbance of mesangial cell regulation in this research project underlies the development of hypertension via altered glomerular hemodynamics including disturbed tubuloglomerular feedback.

本研究的结果包括：1)与正常血压大鼠系膜细胞相比，自发性高血压大鼠(SHR)和Dahl盐敏感型高血压大鼠(DS)的系膜细胞没有增加前列腺素的产生以及细胞外氯浓度降低时钙信号和收缩的减弱；2)胰岛素样生长因子-I受体的激活减弱了正常系膜细胞的钙信号和收缩；3)IGF-I对SHR系膜细胞的钙信号和收缩没有调节作用，但在DS系膜细胞中存在；4)IGF-I对SHR的GFR没有影响，但它增加了正常血压大鼠的GFR；5)Na/H交换器-I仅存在于LLCPK-1细胞的基底外侧；6)β1受体的mRNA表达分析显示其在远端小管表达；7)氯电导存在于兔近端小管的基底外侧。此外，我们提出了我们的假设，即本研究项目中系膜细胞调节障碍是通过肾小球血流动力学改变包括肾小球反馈紊乱而导致高血压的发生。

项目成果

G.Seki et.al.: "Effect of parathyroid hormone on acid-base transport in rabbit proximal tubule S_3 segment." European Journal of Physiology. 423. 7-13 (1993)

G.Seki 等人：“甲状旁腺激素对兔近曲小管 S_3 段酸碱转运的影响。”

N.Noda et al.: "Involvement of rho in GTPγS-induced enhancement of phosphorylation of 20 kDamyosin ligth chair in vascular smooth muscle cells" FEBS Letters. 367. 246-250 (1995)

N.Noda 等人：“rho 参与血管平滑肌细胞中 GTPγS 诱导的 20 kDamyosin ligth chair 磷酸化增强”FEBS Letters 367. 246-250 (1995)。

S.Taniguchi et al: "Distribution of B_2-adrenergic receptor mRNA expresion along the hamster nephror segments" FEBS. 318. 65-70 (1993)

S.Taniguchi 等人：“B_2-肾上腺素受体 mRNA 表达沿仓鼠肾段的分布”FEBS。

K.Nosaka et al: "Permeable typeI collagen membrane promotes glomerular epithelial cell growth on culture" Kidney International. 43. 470-478 (1993)

K.Nosaka 等人：“渗透性 I 型胶原膜促进培养物上的肾小球上皮细胞生长”肾脏国际。

Y.Inishi et al: "Insulin attenuates in tra cellular calccum response and cell contraction caused by vasoactive agents" Kidney International. 45. 1318-1325 (1994)

Y.Inishi 等人：“胰岛素减弱血管活性剂引起的细胞内钙反应和细胞收缩”肾脏国际。