Elucidation of pathological role of NGAL as a modulator of kidney function, metabolism and immune system

阐明 NGAL 作为肾功能、代谢和免疫系统调节剂的病理作用

• 批准号: 23390225
• 负责人: MORI KIYOSHI
• 金额: $ 12.4万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390225/
• 关键词: 腎臓学; 臓器連関; 代謝; 鉄; 炎症; 感染; バイオマーカー; 免疫; 肺; 神経系; 好中球; マクロファージ; 睡眠時無呼吸症候群; 慢性腎臓病; リポカリン; 肥満; 脂肪; 複合体; 存在様式

NGAL KO mice exhibited worsening of adenine nephropathy. 80% of blood NGAL was derived from leukocytes, while urinary NGAL was mainly synthesized by the kidney. In chronic kidney disease, urinary NGAL was partly bound to polyIg receptor or a2-macroglobulin, and showed correlation with severity of renal pathologic changes. Under high fat diet, NGAL KO mice showed resistance against obesity. Hemodialysis patients having low blood NGAL levels showed increased risk to have malnutrition and to develop severe infection. Treatment of WT mice with LPS induced brain inflammation, reduced motor activity and recognition impairment, and these chnges were ameliorated in KO mice. NGAL expression was increased in BAL fluid and lung biopsy samples from patients with idiopathic pulmonary fibrosis.

NGAL KO 小鼠表现出腺嘌呤肾病恶化。血液中80%的NGAL来源于白细胞，而尿液中的NGAL主要由肾脏合成。在慢性肾脏病中，尿NGAL部分与多聚Ig受体或α2-巨球蛋白结合，并与肾脏病理变化的严重程度相关。在高脂肪饮食下，NGAL KO小鼠表现出对肥胖的抵抗力。血液 NGAL 水平较低的血液透析患者营养不良和发生严重感染的风险增加。用 LPS 治疗 WT 小鼠会引起脑部炎症、运动活动减少和识别障碍，而这些变化在 KO 小鼠中得到改善。特发性肺纤维化患者的 BAL 液和肺活检样本中 NGAL 表达增加。

项目成果

Acute disruption of megalin expression in renal cortex reveals compensatory reabsorption capacity of low molecular weight proteins in S3 segment of proximal tubules and collecting ducts

肾皮质巨蛋白表达的急性破坏揭示了近曲小管和集合管 S3 段低分子量蛋白的代偿性重吸收能力

• 作者: KP Mori;K Mori (2nd);et al
• 通讯作者: et al

尿中バイオマーカーの新知見

尿液生物标志物的新发现

• 发表时间: 2011
• 作者: 森潔;向山政志;笠原正登;横井秀基;中尾一和
• 通讯作者: 中尾一和

Blockade of p38 MAPK pathway ameliorates aldosterone-induced renal injury in guanylyl cyclase-A deficient mice

阻断 p38 MAPK 通路可改善鸟苷酸环化酶 A 缺陷小鼠醛固酮诱导的肾损伤

• 发表时间: 2011
• 作者: Kato Y;Mukoyama M;Yokoi H;et al.
• 通讯作者: et al.

Research Group of Diabetic Nephropathy, Ministry of Health, Labour, and Welfare of Japan. Japan Diabetic Nephropathy Cohort Study : study design, methods, and implementation

日本厚生劳动省糖尿病肾病研究组。

• DOI: 10.1007/s10157-013-0778-8
• 发表时间: 2013
• 期刊: Clin Exp Nephrol
• 影响因子: 2.3
• 作者: Furuichi K1;Shimizu M;Toyama T;Koya D;Koshino Y;Abe H;Mori K;Satoh H;Imanishi M;Iwano M;Yamauchi H;Kusano E;Fujimoto S;Suzuki Y;Okuda S;Kitagawa K;Iwata Y;Kaneko S;Nishi S;Yokoyama H;Ueda Y;Haneda M;Makino H;Wada T
• 通讯作者: Wada T

Predictive significance of kidney myeloid-related protein 8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases.

• DOI: 10.1371/journal.pone.0088942
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kuwabara T;Mori K;Kasahara M;Yokoi H;Imamaki H;Ishii A;Koga K;Sugawara A;Yasuno S;Ueshima K;Morikawa T;Konishi Y;Imanishi M;Nishiyama A;Nakao K;Mukoyama M
• 通讯作者: Mukoyama M