Development of novel therapies for cardiovascular diseases by targeting immunosenescence

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15197
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Juntendo University (2020); Niigata University (2019); Keio University (2018)
• Principal Investigator: Shirakawa Kohsuke 順天堂大学, 医学(系)研究科(研究院), 学振特別研究員(PD) (30626388)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: オステオポンチン / 心筋梗塞 / 心不全 / マクロファージ

Outline of Final Research Achievements

We clarified that osteopontin (OPN) plays an essential role in accelerating both reparative fibrosis and clearance of dead cells (efferocytosis) during tissue repair after myocardial infarction (MI) and galectin-3hiCD206+ macrophages is the main source of OPN in post-MI heart. IL(Interleukin)-10-STAT3-galectin-3 axis is essential for Spp1 (encoding OPN) transcriptional activation in cardiac macrophages after MI. Furthermore, we also clarified that IL-10 and M-CSF act synergistically to activate STAT3 and ERK in cardiac macrophages, which in-turn upregulate the expression of galectin-3 and MerTK, leading to the functional maturation of OPN-producing macrophages.

Free Research Field

循環器

Academic Significance and Societal Importance of the Research Achievements

虚血性心不全をはじめとした心不全の予後は進行癌と同様にきわめて予後不良である。
本研究では、心筋梗塞後創傷治癒過程におけるオステオポンチンの役割や産生細胞及びその分化機序を解明した。また、オステオポンチンをコントロールすることにより心筋梗塞後創傷治癒を促進し、心不全の病態を改善させる可能性を示した。