A pathophysiological significance of a novel angiogenesis factor in diabetic kidney disease and chronic kidney disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08730
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Yokohama City University
• Principal Investigator: KANAOKA Tomohiko 横浜市立大学, 附属病院, 助教 (70551258)
• Co-Investigator(Kenkyū-buntansha): 涌井 広道 横浜市立大学, 医学部, 准教授 (10587330) ; 田村 功一 横浜市立大学, 医学研究科, 教授 (40285143)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 糖尿病性腎臓病 / 慢性腎臓病 / 血管新生因子

Outline of Final Research Achievements

Patients with type 2 diabetes mellitus showed increased urinary LRG1 excretion compared to healthy subjects. Furthermore, urinary LRG was positively correlated with albuminuria and negatively correlated with kidney function (eGFR)in patients with type 2 diabetes mellitus. Diabetic model of db/db mice showed increased LRG1 expression in glomerular endothelium compared with control mice, concomitant with the development of diabetic nephropathy. In addition, kidney LRG1 expression was significantly increased in aged mice compared with young mice along with the progression of kidney fibrosis. Similarly, unilateral ureteral obstruction significantly provoked kidney fibrosis and increase in kidney LRG1 expression. Furthermore, we succeeded to generate LRG1 knockout mice.

Free Research Field

糖尿病性腎臓病、慢性腎臓病

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎症モデルマウスの腎におけるmRNA発現トランスクリプトーム解析で明らかになった新規血管新生・増殖系因子、ロイシンリッチα2 糖蛋白質1（LRG1）について、糖尿病性腎臓病や腎線維化の進展とともにその発現が変化することが明らかにされ、腎臓病の病態形成に関与する可能性が示唆された。今後、LRG1ノックアウトマウスを用い、腎臓病の発症・進展におけるLRG1の機能的意義の解明が期待される。 また、尿中LRG1は糖尿病性腎臓病患者の診断・予後予測のバイオマーカーとなる可能性がある。