The Role of Fibrinolytic and Coagulation Factors, a Subset of Angiocrine Factors in Cytokine Storm-Associated Diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08404
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Juntendo University
• Principal Investigator: Hattori Koichi 順天堂大学, 大学院医学研究科, 特任先任准教授 (10360116)
• Co-Investigator(Kenkyū-buntansha): 高橋 聡 東京大学, 医科学研究所, 特任教授 (60226834)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: アンジオクライン因子 / 血管内皮 / プロテアーゼ / バイオマーカー / COVID-19 / 遺伝子発現 / がん増殖 / 核酸製剤

Outline of Final Research Achievements

In this study, the investigators elucidated the mechanisms of cytokine storm generation, cytokine storm syndrome (CSS) severity, and cancer growth by angiocrine factors triggered by vascular endothelial damage. Specifically, using murine models of CSS and cancer, we analyzed human COVID-19 samples, patient information, racial background, disease status, and clinical symptoms, as well as blood levels and activities of angiocrine factors and inflammatory cytokines, including blood coagulation and fibrinolytic factors. Angiocrine factors and inflammatory cytokines were driving tumor growth in murine models. The analysis of blood levels and activities of angiocrine factors, inflammatory cytokines, including fibrinolytic factors and metalloproteinases, endothelial properties, and functions were conducted, suggesting the possibility of early diagnosis of CSS using angiocrine factors as biomarkers. Furthermore, these molecular targets can also serve as novel treatment options for cancer.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

サイトカインストーム症候群(CSS)は、自己免疫疾患や悪性腫瘍、そして最近まで世界中にパンデミックと経済危機をもたらしたCOVID-19に代表される新興・再興感染症の重症化病態と考えられており、極めて予後不良な状態を示唆する。その基礎疾患は、広範囲に渡るだけに、CSSの早期診断と治療法の開発は、人類の存亡を賭けた重要課題と言っても過言ではない。この課題に正面から向き合った本研究の社会的意義は極めて大きいものである。またその一方で、本研究は、各国のトップレベルの施設間連携による国際共同研究として進められ、研究成果はいずれも国際誌上で報告されており、その学術的意義も確固たるものと言えよう。