Role of humoral factors in the development and progression of metabolic syndrome-related kidney diseases

体液因素在代谢综合征相关肾脏疾病发生和进展中的作用

• 批准号: 23591191
• 负责人: MUKOYAMA Masashi
• 金额: $ 3.33万
• 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: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591191/
• 关键词: 腎臓学; 内分泌学; メタボリック症候群; Na利尿ペプチド; アルドステロン; 糖尿病性腎症; 自然炎症; ノックアウトマウス; ナトリウム利尿ペプチド; 肥満関連腎症; toll-like receptor 4

Metabolic syndrome (MetS) represents impaired regulation of humoral or endocrine factors, such as the enhanced renin-angiotensin-aldosterone system. We investigated roles of humoral factors in MetS-associated renal injury.The natriuretic peptide (ANP and BNP) receptor GC-A is abundantly expressed 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 an ARB, antioxidant, or p38 MAPK inhibitor, suggesting their therapeutic potential.In mouse models of diabetes with dyslipidemia, we found that TLR4 and its ligand MRP8, factors associated with homeostatic inflammation, were markedly upregulated together with worsening of nephropathy. Renal injury was significantly alleviated in TLR4-deficient mice. Expression of MRP8 was also enhanced in advanced human diabetic nephropathy, suggesting its role as a prognostic marker.

代谢综合征（MetS）表现为体液或内分泌因素的调节受损，如肾素-血管紧张素-醛固酮系统的增强。我们研究了体液因子在met相关性肾损伤中的作用。利钠肽（ANP和BNP）受体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基因敲除小鼠受到醛固酮和高盐刺激时，观察到大量蛋白尿和明显的足细胞损伤，ARB、抗氧化剂或p38 MAPK抑制剂可以减轻这种损伤，这表明它们具有治疗潜力。在伴有血脂异常的糖尿病小鼠模型中，我们发现与稳态炎症相关的TLR4及其配体MRP8显著上调，同时肾病恶化。tlr4缺陷小鼠的肾损伤明显减轻。MRP8在晚期人类糖尿病肾病中的表达也增强，提示其作为预后标志物的作用。

项目成果

p38 MAPK signaling mediates aldosterone-induced renal injury in natriuretic peptide receptor (GC-A)-deficient mice

p38 MAPK 信号介导利钠肽受体 (GC-A) 缺陷小鼠醛固酮诱导的肾损伤

• 发表时间: 2013
• 作者: Kato Y;Mukoyama M;Yokoi H;et al.
• 通讯作者: et al.

肥満と炎症、レニン・アンジオテンシン系

肥胖与炎症、肾素-血管紧张素系统

• 发表时间: 2012
• 作者: Yao J;Chi Y;Gao K.;向山政志,森潔,桒原孝成,今牧博貴,細田公則,中尾一和
• 通讯作者: 向山政志,森潔,桒原孝成,今牧博貴,細田公則,中尾一和

Peritoneal Fibrosis and High Transport Are Induced in Mildly Pre-injured Peritoneum by 3,4-Dideoxyglucosone-3-ene in Mice

• DOI: 10.3747/pdi.2011.00033
• 发表时间: 2013-03
• 期刊: Peritoneal Dialysis International
• 影响因子: 2.8
• 作者: H. Yokoi;M. Kasahara;K. Mori;T. Kuwabara;Naohiro Toda;R. Yamada;S. Namoto;Takashi Yamamoto;N. Seki;Nozomi Souma;Takuya Yamaguchi;A. Sugawara;M. Mukoyama;K. Nakao

Na利尿ペプチドとNgal-最新の話題-

利尿肽和Ngal-最新话题-

• 发表时间: 2011
• 作者: Yan QJ;et al.;向山政志,森潔,笠原正登,中尾一和
• 通讯作者: 向山政志,森潔,笠原正登,中尾一和

Do statins play a role in renoprotection?

他汀类药物在肾脏保护中发挥作用吗？

• DOI: 10.1007/s10157-013-0928-z
• 发表时间: 2014
• 期刊: Ueshima K. Clin Exp Nephrol
• 作者: Kasahara M;Nakagawa T;Yokoi H;Kuwabara T;Yasuno S;Mori K;Mukoyama M
• 通讯作者: Mukoyama M