Development of a new treatment for diabetic nephropathy by siRNA delivery using nanocarriers

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19533
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Toshiro Fujita 東京大学, 先端科学技術研究センター, 名誉教授 (10114125)
• Co-Investigator(Kenkyū-buntansha): 丸茂 丈史 東京大学, 先端科学技術研究センター, 特任准教授 (70265817)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: 糖尿病性腎症 / エピジェネティクス / DNAメチル化

Outline of Final Research Achievements

Because the progression of diabetic nephropathy is difficult to interfere with, it was thought that epigenetic modifications to renal constituent cells were involved in its development, but the details were unclear. In this study, we show that DNA methylation of the promoter of the Tgfb1 gene, which induces fibrosis and inflammation, occurs in renal mesangium cells of diabetic mouse models, and that the increased expression of the Tgfb1 gene is involved in the progression of nephropathy, indicating a new mechanism of diabetic nephropathy progression. A series of studies showed that cell-specific DNA methylation of the kidney is a promising predictive marker as well as a therapeutic target for diabetic nephropathy.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、糖尿病性腎症の進行には腎構成細胞におけるエピジェネティック修飾が深く関与することを証明した。すなわち糖尿病性腎症の抑制のためには、エピジェネティク治療薬の開発と共に、有用な早期マーカーの探索とそれによる予防が重要であることを実証したものであり、糖尿病による腎機能障害の医療に貢献するものと期待される