Elucidation of regulatory mechanism of cytosolic mitochondrial DNA in cardiac injury and its therapeutic application

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22622
• 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: Kyushu University
• Principal Investigator: Tsutsui Hiroyuki 九州大学, 医学研究院, 教授 (70264017)
• Co-Investigator(Kenkyū-buntansha): 松島 将士 九州大学, 大学病院, 助教 (80552869) ; 井手 友美 九州大学, 医学研究院, 准教授 (90380625)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 心不全 / ミトコンドリアDNA / 炎症

Outline of Final Research Achievements

In failing hearts and mitochondrial DNA-treated cardiomyocytes, ZBP1 protein levels were increased. ZBP1 knockout mice demonstrated exacerbation of cardiac dysfunction, accompanied by elevation of inflammatory cytokines and NF-kB. In addition, the inhibition of TLR9 decreased ZBP1 protein levels. ZBP1 is positively regulated by TLR9. ZBP1 plays a protective role in cardiac inflammation and injury by negatively regulating NF-kB pathway.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究は心筋細胞における新たな炎症制御機構を明らかにすることで心不全の病態理解を進め、新たな治療法の確立へと発展する可能性がある。