Pathophysiological analysis for tissue renin-angiotensin-system using Cre-loxP system

使用 Cre-loxP 系统对组织肾素-血管紧张素系统进行病理生理学分析

• 批准号: 16590704
• 负责人: UMEMURA Satoshi
• 金额: $ 2.18万
• 依托单位: Yokohama City University (YCU)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590704/
• 关键词: Angiotensinogen; Kidney; Tissue renin-angiotensin-system; Mice; 組織レニン-アンジオテンシン系

Generation of loxP-franked (floxed) angiotensinogen mice.The conditional angiotensinogen knockout construct was used to generate floxed angiotensinogen mice. Heterozygous mice were bred to generate homozygous mice.Pathophysiological analysis of tissue renin-angiotensin-systemWe examined the role of the renin-angiotensin system (RAS) in the regulation of macula densa cyclooxygenase-2 (COX-2) during altered dietary salt intake using Atg-/- mice. This study demonstrated that COX-2 activity in the macula densa can be regulated by salt intake through a mechanism independent of the RAS, and COX-2 expression is functionally linked to renal cortical N-NOS activity in Atg-/- mice (Nephron Physiol.2006).The effects of altered dietary salt intake on renal endothelial nitric oxide synthase (eNOS) expression were determined in angiotensin type-1a receptor gene knockout (AT1a-/-) mice and Atg-/- mice. This study demonstrated that AT1a receptor-mediated inputs play critical roles in maintaining renal vascular eNOS expression and activity during changes in salt-water balance and systemic BP (J Am Soc Nephrol, 2004, Cell Tissue Res, 2006).We examined the distribution of AT1 receptor-associated protein in nephron segments (Kidney Int,2006).We evaluated the effect of angiotensin II on the pathogenesis of immune mediated colitis using Atg-/-. This study revealed that RAS is involved in the immune system in the colon (Gut,2005).These results demonstrated that an antagonism of the RAS is a potential prophylactic strategy for the treatment of tissue damage.

条件性血管紧张素原基因敲除小鼠被用于产生血管紧张素原基因。组织肾素-血管紧张素系统的病理生理学分析我们利用ATG-/-小鼠研究了肾素-血管紧张素系统(RAS)在改变饮食盐摄入量过程中对致密斑环氧合酶-2(COX-2)的调节作用。这项研究表明，致密斑内COX-2活性可以通过独立于RAS的机制被盐摄入调节，并且COX-2的表达在功能上与ATG-/-小鼠的肾皮质N-NOS活性有关(Nephron Physiol.2006)。在血管紧张素-1a受体基因敲除(AT1a-/-)小鼠和ATG-/-小鼠中，研究了饮食盐摄入量改变对肾内皮细胞一氧化氮合酶(ENOS)表达的影响。本研究证实了AT1a受体介导的信息输入在维持肾血管eNOS表达和活性方面起着关键作用，尤其是在盐水平衡和全身血压变化中(J Am Soc Nephrol，2004，Cell Organization RES，2006)。我们研究了AT1受体相关蛋白在肾单位节段的分布(Kidney Int，2006)。我们利用ATG-/-评估血管紧张素II在免疫介导性结肠炎发病机制中的作用。这项研究表明RAS参与了结肠的免疫系统(Gut，2005)。这些结果表明，拮抗RAS是治疗组织损伤的一种潜在的预防性策略。

项目成果

Expression of endothelial nitric oxide synthase is suppressed in the renal vasculature of angiotensinogen-gene knockout mice.

血管紧张素原基因敲除小鼠的肾血管系统中内皮一氧化氮合酶的表达受到抑制。

• 发表时间: 2006
• 期刊: Cell Tissue Res. 323
• 作者: Kihara M;et al.
• 通讯作者: et al.

合併症を伴う高血圧の治療.循環器疾患最近の治療

高血压合并症的治疗。心血管疾病的近期治疗

• 发表时间: 2006
• 作者: 田中秀央;高松哲郎;梅村敏
• 通讯作者: 梅村敏

Alterations in renal endothelial nitric oxide synthase expression by salt diet in angiotensin type-1a receptor gene knockout mice

血管紧张素1a型受体基因敲除小鼠盐饮食对肾内皮一氧化氮合酶表达的影响

• 发表时间: 2004
• 期刊: J Am Soc Nephrol 15
• 作者: Sato K;et al.
• 通讯作者: et al.

Nuclear receptor LXRalpha is involved in cAMP-mediated human renin gene expression.

核受体 LXRα 参与 cAMP 介导的人肾素基因表达。

• DOI: 10.1016/j.mce.2004.07.005
• 发表时间: 2004
• 期刊: Molecular and cellular endocrinology
• 影响因子: 4.1
• 作者: Tamura,Kouichi;Chen,YuqingE;Tanaka,Yutaka;Sakai,Masashi;Tsurumi,Yuko;Koide,Yuichi;Kihara,Minoru;Pratt,RichardE;Horiuchi,Masatsugu;Umemura,Satoshi;Dzau,VictorJ
• 通讯作者: Dzau,VictorJ

Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo

• DOI: 10.1074/jbc.m404149200
• 发表时间: 2004-06-18
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Ishida, J;Hashimoto, T;Fukamizu, A
• 通讯作者: Fukamizu, A