The regulation of Inflammatory process via HIF-alpha

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19372
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Semba Hiroaki 東京大学, 医学部附属病院, 登録研究員 (80747923)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 低酸素 / 炎症 / マクロファージ

Outline of Final Research Achievements

Hypoxia is a pathological condition in which the tissue is deprived of adequate oxygen supply, occurring in many cardiovascular diseases. Each cell exerts its own responses to hypoxia, and most of them are mediated through a transcription factor, hypoxia inducible factor 1α (HIF-1α). Macrophages, a key mediator of inflammation, migrate to such hypoxic areas, and HIF-1α - mediated hypoxic responses of macrophage strongly accelerate the inflammation processes. While we previously showed that HIF-1α plays a key role in inflammatory mediator production in severely hypoxic areas, the role of hypoxia signaling in the migratory capacity of inflammatory cells remains unclear. In this study, I found a novel function of HIF-1α- PDK1 - mediated glycolytic reprogramming in macrophage migratory capacity, and suggest that targeting the function of PDK1 could represent a potential therapeutic approach to suppressing inflammatory cell recruitment.

Free Research Field

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