The elucidation of the pathophysiology of cardiorenal syndrome by targeting metabolic reprogramming in proximal tubular epithelial cells.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16096
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Keio University (2022-2023); Juntendo University (2021)
• Principal Investigator: Shirakawa Kohsuke 慶應義塾大学, 医学部(信濃町), 助教 (30626388)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 生活習慣病 / マクロファージ

Outline of Final Research Achievements

We conducted pathophysiological research involving osteopontin (OPN), which is associated with heart diseases such as heart failure and myocardial infarction, as well as kidney disease, diabetes, and pulmonary fibrosis. Using Spp1-EGFP Knock-in reporter mice, I elucidated that organ-specific OPN-producing cells appeared in models of myocardial infarction, aortic valve stenosis, obesity, renal fibrosis after unilateral renal artery ligation, and pulmonary fibrosis, exacerbating the respective pathologies. The cell-cell interaction analysis of single-cell RNA-seq data from multiple organs related to lifestyle diseases such as aortic valve stenosis, post-infarcted heart, visceral fat of obese patients, kidneys of chronic kidney disease patients, and lungs of pulmonary fibrosis patients, I clarified the pathogenic exacerbation mechanisms via OPN signaling.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

OPNは生理的に生体恒常性を維持する作用もあるためOPNを直接治療標的とすることは難しく、疾患臓器特異的に特定の細胞から不適切に産生されるOPNの産生制御機構を解明できれば、OPNを標的とした生活習慣病の治療法開発に繋がる可能性がある。本研究の将来展望として生活習慣病患者の健康寿命の延伸のみならず、生活習慣病に関連する循環器病疾患の入院や手術費等を抑制でき医療経済的にも国民に還元できる可能性がある。