structure of prorenin molecule

肾素原分子的结构

• 批准号: 17390249
• 负责人: ICHIHARA Atsuhiro
• 金额: $ 10.51万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390249/
• 关键词: prorenin; (pro)renin receptor; diabetes; kidney; renin-angiotensin system; プロレニン受容体

In 2005, using streptozotocin-induced diabetic angiotensin-II-type-1-receptor-deficient-mice, we provided the evidence that angiotensin II-independent pathway caused by binding of human prorenin to human (pro)renin receptor significantly contributes to the development and progression of diabetic nephropathy. In 2006, using human cultured vascular smooth muscle cells, we observed the localization of human (pro)renin receptor in the cytosol close to nucleus and its transposition into the nucleus by the load of prorenin. In addition, rat prorenin was capable of binding to human (pro)renin receptor and thus stimulating the receptor-dependent intracellular signals but was not activated by binding to human (pro)renin receptor. In human vascular smooth muscle cells, human prorenin stimulated the MAP kinase pathways, leading to cell proliferation, through binding to human (pro)renin receptor independently of angiotensin II. In 2007, we developed human-(pro)renin-receptor-transgenic rats which have no enhanced tissue renin-angiotensin system because rat prorenin is incapable of being activated by binding to human (pro)renin receptor. However, the human-(pro)renin-receptor-transgenic rats had an enhanced (pro)renin receptor-dependent intracellular signaling pathways, and slowly progressive nephropathy, that is glomerulosclerosis with proteinuria developed in the transgenic rats. The development of nephropathy occurred in the transgenic rats was caused by the receptor-dependent MAP kinase pathways and was independent of blood pressure or renal angiotensin II levels. Thus, the human-(pro)renin-receptor-transgenic rats was thought to be useful for studying the signals of human(pro)renin receptor in vivo.

2005年，我们利用链脲佐菌素诱导的糖尿病血管紧张素- ii型1受体缺陷小鼠，证明了人prorenin与人（pro）肾素受体结合引起的血管紧张素- ii独立通路在糖尿病肾病的发生和进展中起着重要作用。2006年，我们利用培养的人血管平滑肌细胞，观察到人肾素受体在靠近细胞核的细胞质中定位，并在原肾素负荷下转位到细胞核内。此外，大鼠prorenin能够与人肾素受体结合，从而刺激受体依赖性的细胞内信号，但不被人肾素受体激活。在人血管平滑肌细胞中，人前肾素通过独立于血管紧张素II与人（前）肾素受体结合，刺激MAP激酶通路，导致细胞增殖。2007年，我们开发了人肾素受体转基因大鼠，由于大鼠的原肾素不能通过与人肾素受体结合而被激活，因此没有增强的组织肾素血管紧张素系统。然而，人肾素受体转基因大鼠具有增强的肾素受体依赖的细胞内信号通路，并且在转基因大鼠中发生缓慢进行性肾病，即肾小球硬化伴蛋白尿。转基因大鼠肾病的发生是由受体依赖性MAP激酶途径引起的，与血压或肾血管紧张素II水平无关。因此，转基因人肾素受体大鼠可用于研究人肾素受体的体内信号。

项目成果

Nonproteolytically activated prorenin promotes pathologic, but not physiologic, retinal neovascularization

非蛋白水解激活的肾素原促进病理性而非生理性视网膜新生血管形成

• 发表时间: 2007
• 作者: Satofuka S. Ichihara A;Nagai N;Koto T;Shinoda H;Ozawa Y;Tsubota K;Itoh H;Oike Y;Ishida S
• 通讯作者: Ishida S

Cilnidipine and Telmisartan Similarly Improves Vascular Damage in Hypertensive Patients

西尼地平和替米沙坦同样可以改善高血压患者的血管损伤

• 发表时间: 2007
• 期刊: Clinical Medicine: Cardiology 1
• 作者: Uruno A;et al.;S.Satofuka;A.Ichihara;H.Takahashi;A.Ichihara;Y.Kaneshiro
• 通讯作者: Y.Kaneshiro

Prorenin receptor blockade inhibits development of glomerulosclerosis in dia-betic angiotensin II type la receptor deficient mice

肾素原受体阻断可抑制糖尿病血管紧张素 II 型 Ia 受体缺陷小鼠肾小球硬化的发展

• 发表时间: 2006
• 期刊: J Am Soc Nephrol 17
• 作者: Y.;Kaneshiro;S. Satofuka;Y. Kaneshiro;H. Takahashi;A. Ichihara;M. Sakoda;A.Ichihara;S.Satofuka;A.Ichihara;A.Ichihara
• 通讯作者: A.Ichihara

プロレニンと(プロ)レニン受容体

肾素原和肾素原受体

• 发表时间: 2007
• 作者: A.;Ichihara;A. Ichihara;A. Ichihara;A.Ichihara;A.Ichihara;M.Sakoda;市原 淳弘;脇野 修;市原 淳弘;市原 淳弘;迫田 万里代;市原 淳弘;猪股 研太;市原 淳弘;市原 淳弘
• 通讯作者: 市原 淳弘

高脂肪食負荷ヒト(プロ)レニン受容体高発現ラットにおける内臓肥満と耐糖能障害

高脂肪饮食喂养的人肾素原受体高表达大鼠的内脏肥胖和葡萄糖不耐症

• 发表时间: 2007
• 作者: A.;Ichihara;A. Ichihara;A. Ichihara;A.Ichihara;A.Ichihara;M.Sakoda;市原 淳弘;脇野 修;市原 淳弘;市原 淳弘;迫田 万里代;市原 淳弘;猪股 研太;市原 淳弘;市原 淳弘;高橋 秀奈
• 通讯作者: 高橋 秀奈