Role of purinergic signaling on macrophage function induced by stretch-mediated mechanical stimulation.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16010
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Takasaki University of Health and Welfare
• Principal Investigator: ito masaaki 高崎健康福祉大学, 薬学部, 准教授 (30438759)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: マクロファージ / 機械的進展刺激 / プリン作動性シグナル / MCP-1 / P2Y6受容体

Outline of Final Research Achievements

Macrophages, immune cells, are involved in a variety of inflammatory diseases. This study analyzed the effects of mechanical stretch stimulus on macrophage function. Mechanical stretch loading on macrophages resulted in the secretion of extracellular nucleotides such as adenosine triphosphate (ATP) and increased gene expression levels of chemokines such as monocyte chemoattractant protein-1 (MCP-1) in a P2Y6 receptor-dependent manner, which is one of the nucleotide receptors. In addition, the activation of protein kinases such as ERK and p38 was observed in the cells upon mechanical stress load. In particular, the activation of the ERK pathway was involved in the increased gene expression and protein production of MCP-1. These findings suggest that macrophages may be activated when they sense mechanical stress in the heart, lungs, or intestine, and may promote inflammatory responses and contribute to pathogenesis.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

近年、我々の健康維持や疾患に物理的な力による調節が深く関わっていることが示唆されている。本研究では免疫担当細胞の一つであるマクロファージに焦点を当て心臓や肺、腸などの組織で受容する機械的な刺激の影響を検討した。マクロファージは、機械的刺激の負荷に応じて炎症性サイトカインや白血球遊走因子の発現を上昇させ炎症応答を促進する可能性が明らかとなった。本研究成果は、マクロファージがダイナミックな機械的刺激を受容する組織における病態、すなわち動脈硬化や肺や腸の炎症、心筋梗塞などのような病態の理解と新たな治療戦略の提示につながると期待される。