Translational research and clinical application of the natriuretic peptide system in the kidney.

利尿钠肽系统在肾脏中的转化研究及临床应用。

• 批准号: 20590956
• 负责人: MUKOYAMA Masashi
• 金额: $ 3万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590956/
• 关键词: 腎臓学; 慢性賢臓病; トランスレーショナルリサーチ; Na利尿ペプチド; ノックアウトマウス; アルドステロン; 糖尿病性賢症; 蛋白尿; ポドサイト; 慢性腎臓病; トランスジェニックマウス; 糖尿病性腎症; 結合組織成長因子(CTGF); 線維化

Natriuretic peptide family (ANP, BNP, and CNP) exert potent diuretic, natriuretic and vasorelaxing properties, as well as the inhibition of the renin-angiotensin-aldosterone system. We investigated the role of natriuretic peptides in renal disease and its complications.1. Preparation of CNP-transgenic mice (CNP-Tg) and effects of CNP on renal injury :CNP acts as a local hormone in the vessel, bone and kidney. Human SAP promoter-driven CNP-Tg exhibited enhanced bone growth as a result of excess circulating CNP. CNP-Tg showed ameliorated renal fibrosis and macrophage infiltration upon obstructive nephropathy model.2. Role of GC-A (a receptor for ANP and BNP) and aldosterone in glomerular injury :GC-A is expressed abundantly in renal tubules, but its role in glomerular injury is unknown. When GC-A knockout mice were subjected to aldosterone and high salt, massive proteinuria with marked podocyte injury was observed, which was alleviated with the MR antagonist, ARB or antioxidant.3. Role of ANP and BNP in peritoneal sclerosis :Peritoneal sclerosis is a serious complication in chronic peritoneal dialysis, but the effective treatment is not established yet. Subcutaneous ANP administration as well as chronic BNP excess in transgenic mice effectively ameliorated peritoneal adhesion in a mouse model of peritoneal sclerosis.These results indicate that natriuretic peptides will have a various therapeutic potential in renal disease and related pathophysiological conditions.

利钠肽家族（ANP、BNP和CNP）具有利尿、利钠和舒张血管的作用，并能抑制肾素-血管紧张素-醛固酮系统。我们研究了利钠肽在肾脏疾病及其并发症中的作用。CNP转基因小鼠（CNP-Tg）的制备和CNP对肾损伤的影响：CNP在血管、骨和肾脏中作为局部激素发挥作用。人SAP启动子驱动的CNP-Tg由于过量的循环CNP而表现出增强的骨生长。结论：1. CNP-Tg能改善梗阻性肾病模型大鼠肾纤维化和巨噬细胞浸润. GC-A（ANP和BNP的受体）和醛固酮在肾小球损伤中的作用：GC-A在肾小管中大量表达，但其在肾小球损伤中的作用尚不清楚。当GC-A基因敲除小鼠接受醛固酮和高盐时，可观察到大量蛋白尿和明显的足细胞损伤，MR拮抗剂、ARB或抗氧化剂可减轻这种损伤. ANP和BNP在腹膜硬化中的作用：腹膜硬化是慢性腹膜透析的严重并发症，但目前尚无有效的治疗方法。转基因小鼠皮下注射ANP和慢性BNP过量有效地改善了腹膜硬化小鼠模型的腹膜粘连，这些结果表明利钠肽在肾脏疾病和相关病理生理条件下具有各种治疗潜力。

项目成果

Podocyte-specific expression of tamoxifen-inducible Cre recombinase in mice

• DOI: 10.1093/ndt/gfq029
• 发表时间: 2010-07-01
• 期刊: NEPHROLOGY DIALYSIS TRANSPLANTATION
• 影响因子: 6.1
• 作者: Yokoi, Hideki;Kasahara, Masato;Nakao, Kazuwa
• 通讯作者: Nakao, Kazuwa

Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to gelomeruli, proximal tubules, and distal nephrons.

尿中性粒细胞明胶酶相关脂质运载蛋白水平反映了肾小球、近端肾小管和远端肾单位的损伤。

• 发表时间: 2009
• 期刊: Kidney International 75
• 作者: Takashige Kuwabara;et al.
• 通讯作者: et al.

Overexpression of connective tissue growth factor in podocytes worsens diabetic neohropathy in mice.

足细胞中结缔组织生长因子的过度表达会加重小鼠糖尿病肾病。

• 发表时间: 2008
• 期刊: Kidney International 73
• 作者: Hideki Yokoi;et al.
• 通讯作者: et al.

Natriuretic peptide receptor guanylyl cyclase-A signaling exerts antagonistic effects on the local renin-angiotensin- aldosterone system in kidney.

利钠肽受体鸟苷酸环化酶-A 信号传导对肾脏局部肾素-血管紧张素-醛固酮系统产生拮抗作用。

• 发表时间: 2010
• 作者: Ogawa Y;Mukoyama M;Yokoi H;Kasahara M;Mori K;Yoshioka T;Saito Y;Kuwabara T;Imamaki H;Kawanishi T;Koga K;Ishii A;Kishimoto I;Sugawara A;Nakao K
• 通讯作者: Nakao K

Searching for novel intercellular signal-transducing molecules in the kidney and their clinical application.

寻找肾脏中新型细胞间信号转导分子及其临床应用。

• 发表时间: 2010
• 期刊: Clin Exp Nephrol.
• 作者: Mori K;Mukoyama M;Nakao K.
• 通讯作者: Nakao K.