Effect of salt load on the intrarenal angiotensin activity and receptor-mediated prorenin system in kidney fibrosis

盐负荷对肾纤维化肾内血管紧张素活性及受体介导的肾素原系统的影响

• 批准号: 20590967
• 负责人: YAMAMOTO Tatsuo
• 金额: $ 3万
• 依托单位: Hamamatsu 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-20590967/
• 关键词: レニン・アンジオテンシン系; 高塩分; プロレニン; 腎線維化; アンジオテンシン; レニン; (プロ)レニン受容体; 塩分摂取; 慢性腎臓病; プロレニン受容体; 閉塞性腎障害

Although activation of intrarenal renin angiotensin system (RAS) is involved in the progression of kidney fibrosis, it is unknown how salt load that suppresses circulating RAS aggravates kidney fibrosis. This study demonstrated that high salt intake increased the apical membranous transition of (pro)renin receptor in collecting ducts and connecting tubules, resulting in the increased binding of prorenin and renin proteins without concomitant renin mRNA expression, followed by non-proteolytic activation of prorenin and angiotensin II generation, with resultant worsening of renal fibrosis in chronic anti-thymocyte serum nephritis on high salt intake.

尽管肾内肾素血管紧张素系统（RAS）的激活与肾纤维化的进展有关，但抑制循环RAS的盐负荷如何加剧肾纤维化尚不清楚。这项研究表明，高盐摄入量增加了集合管和连接小管中肾素（原）受体的顶膜转变，导致肾素原和肾素蛋白结合增加，但不伴随肾素mRNA表达，随后非蛋白水解激活肾素原和血管紧张素II生成，导致慢性抗胸腺细胞血清中肾纤维化恶化 肾炎与高盐摄入有关。

项目成果

Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury.

• DOI: 10.1038/ki.2010.141
• 发表时间: 2010-08
• 期刊: KIDNEY INTERNATIONAL
• 影响因子: 19.6
• 作者: Schneider, Markus P.;Sullivan, Jennifer C.;Wach, Paul F.;Boesen, Erika I.;Yamamoto, Tatsuo;Fukai, Tohru;Harrison, David G.;Pollock, David M.;Pollock, Jennifer S.
• 通讯作者: Pollock, Jennifer S.

Reduction of transforming growth factor-β type II receptor is caused by the enhanced ubiquitin-dependent degradation in human renal cell carcinoma

• DOI: 10.1002/ijc.25164
• 发表时间: 2010-10-01
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Fukasawa, Hirotaka;Yamamoto, Tatsuo;Hishida, Akira
• 通讯作者: Hishida, Akira

Decrease in tumor necrosis factor-alpha receptor-associated death domain results from ubiquitin-dependent degradation in obstructive renal injury in rats

大鼠梗阻性肾损伤中肿瘤坏死因子-α受体相关死亡结构域的减少是由泛素依赖性降解造成的

• 发表时间: 2009
• 期刊: Am.J.Pathol. 175
• 作者: Misaki T;Yamamoto T;Suzuki S;Fukasawa H;Togawa A;Ohashi N;Suzuki H;Fujigaki Y;Oda T;Uchida C;Kitagawa K;Hattori T;Kitagawa M;Hishida A
• 通讯作者: Hishida A

Angiotensin (1-7) receptor antagonism equalizes angiotensin II-induced hypertension in male and female spontaneously hypertensive rats.

• DOI: 10.1161/hypertensionaha.110.153668
• 发表时间: 2010-10
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Sullivan JC;Bhatia K;Yamamoto T;Elmarakby AA
• 通讯作者: Elmarakby AA

Role of Rho-kinase (ROCK) and epidermal growth factor receptor (EGFR) activation in glomerular injuries induced by AngiotensinII (AngII)-dependent hypertension.

Rho 激酶 (ROCK) 和表皮生长因子受体 (EGFR) 激活在血管紧张素 II (AngII) 依赖性高血压引起的肾小球损伤中的作用。

• 发表时间: 2010
• 作者: Suzuki H;et al.
• 通讯作者: et al.