Development of the novel therapeutic strategy for diabetic nephropathy through anti-inflammatory effects.

通过抗炎作用开发糖尿病肾病的新治疗策略。

• 批准号: 21591031
• 负责人: SHIKATA Kenichi
• 金额: $ 2.91万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591031/
• 关键词: 腎臓病学; 糖尿病性腎症; microinflammation; osteopontin; cholecystokinin; 炎症; 糖尿病; マクロファージ; Cholecystokinin; Osteopontin

We have demonstrated that low grade inflammation, microinflammation, is involved in the pathogenesis of diabetic nephropathy as well as of atherosclerosis. We have recently reported that anti-inflammatory agents such as statin and thiazolidinedione show renoprotective effects through anti-inflammatory actions in diabetic animals. In this study, 1) We induced diabetes into osteopontin knockout(KO) mice. Osteopontin KO mice showed the improvement of tissue injuries and inflammatory reactions in the kidney. 2) We found that GLP-1 receptor is expressed on monocte/macrophage and glomerular endothelial cells. GLP-1 receptor agonist showed renoprotective effects on diabetic rats through anti-inflammatory actions. These results suggest that osteopontin play a role in the pathogenesis of diabetic nephropathy and GLP-1 receptor agonist might be beneficial for the treatment of diabetic nephropathy.

我们已经证明，低度炎症，微炎症，参与糖尿病肾病以及动脉粥样硬化的发病机制。我们最近报道，抗炎药，如他汀类药物和噻唑烷二酮显示肾脏保护作用，通过抗炎作用在糖尿病动物。在本研究中，1）我们诱导糖尿病骨桥蛋白基因敲除（KO）小鼠。骨桥蛋白基因敲除小鼠显示肾脏组织损伤和炎症反应的改善。2)我们发现GLP-1受体在单核细胞/巨噬细胞和肾小球内皮细胞上表达。GLP-1受体激动剂通过抗炎作用对糖尿病大鼠肾脏有保护作用。提示骨桥蛋白在糖尿病肾病的发病中起一定作用，GLP-1受体激动剂可能对糖尿病肾病的治疗有益。

项目成果

糖尿病性腎症の成因としてのMicroinflammation

微炎症是糖尿病肾病的一个原因

• 发表时间: 2010
• 作者: Tanaka K;四方賢一
• 通讯作者: 四方賢一

Cholecystokinin plays a novel protective role in diabetic kidney through anti-inflammatory actions on macrophage. -anti-inflammatory effect of CCK-

胆囊收缩素通过对巨噬细胞的抗炎作用在糖尿病肾脏中发挥新的保护作用。

• 发表时间: 2012
• 期刊: Diabetes
• 影响因子: 7.7
• 作者: Ogasawara S;et al.;柳田素子;Okamoto I;宮本聡
• 通讯作者: 宮本聡

Cholecystokinin amelioratesdia betic renal injuries via anti-inflam matory effects

胆囊收缩素通过抗炎作用改善糖尿病肾损伤

• 发表时间: 2009
• 作者: Okamoto I;Shoichi Maruyama;Miyamoto S Shikata K Sasaki M Nishishita S Sato C Kataoka H Kodera R Hirota D Kajitani N Makino H
• 通讯作者: Miyamoto S Shikata K Sasaki M Nishishita S Sato C Kataoka H Kodera R Hirota D Kajitani N Makino H

Phenotypic change of macrophages in the progression of diabetic nephropathy; sialoadhesin-positive activated macrophages are increased in diabetic kidney

• DOI: 10.1007/s10157-012-0625-3
• 发表时间: 2012-04
• 期刊: Clinical and Experimental Nephrology
• 影响因子: 2.3
• 作者: Ryo Nagase;Nobuo Kajitani;K. Shikata;D. Ogawa;Ryo Kodera;S. Okada;Y. Kido;H. Makino

Advanced Glycation End Products Subspecies-Selectively Induce Adhesion Molecule Expression and Cytokine Production in Human Peripheral Blood Mononuclear Cells

• DOI: 10.1124/jpet.109.150581
• 发表时间: 2009-07-01
• 期刊: JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
• 影响因子: 3.5
• 作者: Takahashi, Hideo Kohka;Mori, Shuji;Nishibori, Masahiro
• 通讯作者: Nishibori, Masahiro