;The roles of hypoxia signaling in the pathogenesis of lifestyle related diseases

2018 Fiscal Year Final Research Report

• Project Area: Oxygen biology: a new criterion for integrated understanding of life
• Project/Area Number: 26111003
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: Nangaku Masaomi 東京大学, 医学部附属病院, 教授 (90311620)
• Co-Investigator(Kenkyū-buntansha): 合田 亘人 早稲田大学, 理工学術院, 教授 (00245549) ; 武田 憲彦 東京大学, 医学部附属病院, 助教 (40422307)
• Project Period (FY): 2014-07-10 – 2019-03-31
• Keywords: 生活習慣病 / 低酸素 / 慢性腎臓病 / 肝臓病 / 心臓病 / 炎症 / 線維化

Outline of Final Research Achievements

Kidney, liver or heart consumes a large amount of molecular oxygen to maintain its activity, thus oxygen availability in each organ could influence its function. The molecular link, however, between hypoxic environment and the disease progression has not been fully elucidated.
In this study, we examined the roles of hypoxia inducible factor (HIF)-1alpha; signaling during the pathogenesis of lifestyle related diseases including chronic kidney disease, drug-induced liver injury and heart failure. Based on the in vivo animal models, we identified part of the critical pathways which augment the disease progression. In addition, we established a phosphorescence-based technology where we could measure tissue oxygen concentration quantitatively. These results will help us to gain a novel insight into the pathogenesis of lifestyle related disorders.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

本研究により慢性腎臓病、薬剤性肝障害、心不全の病態進展における低酸素シグナルの役割を明らかにすると共に将来的な治療標的候補を同定した。今後、新たな生活習慣病治療介入への応用が期待される。併せて本研究では腎臓における組織酸素濃度の定量的計測を可能にする新規燐光プローブを用いた解析法を開発した。この手法は腎臓体内の各臓器への応用が可能であり、今後の酸素生物学の進展における重要な技術的基盤になると考えられる。