the mechanism of albumin reabsorption moduleted by macrophage driving proxymal tubules damage in diabetic kidney

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15981
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Nara Medical University
• Principal Investigator: Eriguchi Masahiro 奈良県立医科大学, 医学部, 講師 (40572102)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: アンジオテンシン変換酵素 / マクロファージ

Outline of Final Research Achievements

We examined streptozotocin induced diabetes model with ACE 10/10 mice lacking ACE expression in renal tubules and endothelial cells, which are the main sources of ACE expression in the kidney, but expressing ACE only in macrophages.
The absence of intra-renal ACE normalized the glomerular hypertrophy and glomerular hyperfiltration in diabetic ACE 10/10 mice. However, these mice developed mesangial expansion, tubular injury, and albuminuria that were similar to that observed in diabetic wild-type mice. The studies using macrophage cell line; Raw 264.7 and mouse-ACE overexpressing plasmid confirmed that LPS-induced IL-6 and nitric oxide release from macrophages overexpressing ACE was significantly higher than those from macrophage treated with control vector. The migration ability of macrophages overexpressing ACE was also significantly higher than that of control vector-expressing cells.

Free Research Field

糖尿病性腎臓病

Academic Significance and Societal Importance of the Research Achievements

糖尿病ではマクロファージにおけるACE発現は増加しており、ストレプトゾトシン誘発性糖尿病性腎臓病におけるアルブミン尿および尿細管間質性線維症の発症に重要な役割を果たしていた。