Exploration of mechanisms involved in epigenetic abnormality in diabetic kidney disease using single cell analysis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K15466
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Marumo Takeshi 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): 2016-04-01 – 2019-03-31
• Keywords: 糖尿病性腎症 / DNAメチル化 / エピジェネティクス

Outline of Final Research Achievements

The levels of blood glucose in the early stage of diabetes have been shown to determine the development of diabetic kidney disease (DKD) later in life. Epigenetic mechanisms are suggested to be involved in this memory phenomenon. We investigated the possibility to utilize epigenetic information of the kidney for new diagnosis and treatment of DKD. We found nuclear receptor Pxr and fibrogenic factor TGF-beta are demethylated in the kidneys of diabetic mice, revealing the candidates of therapeutic targets. We also showed that the levels of kidney signature DNA methylation in urine sediment correlate with kidney function decline in diabetic patients. Epigenetic urinalysis may serve as a novel diagnostic strategy for DKD.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎症は透析原因疾患の第一位であり、新たな診断・治療法を開発する必要がある。記憶の保持に関わるエピジェネティクスの観点から検討することにより、糖尿病性腎症の発症と進行に関わる重要な経路が解明できると思われた。本研究でその候補となる複数の経路が明らかにされ、ヒトでの実証と病的意義の証明が今後必要である。さらに、糖尿病症例の尿DNAメチル化解析が、新たな尿診断の手法になる可能性を提示することができ、エピジェネティック尿検査の実現性について今後検討を進める予定である。