Neurogenic peptide-mediated pathogenetic control and therapeutic application in septic DIC

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17855
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Tokyo Medical and Dental University (2022-2023); University of Miyazaki (2020-2021)
• Principal Investigator: Suekane Akira 東京医科歯科大学, 東京医科歯科大学病院, 助教 (40856382)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 敗血症 / DIC

Outline of Final Research Achievements

Disseminated intravascular coagulation (DIC) is a frequent complication of sepsis and significantly worsens prognosis. In this study, we aimed to clarify the role of CGRP in septic DIC and to examine its potential application as a therapeutic target. We generated a mouse model of septic DIC, administered CGRP inhibitors, and examined the effects of CGRP inhibitors on intracellular signaling using cell lines. We found that telcagepant (MK-0974), an inhibitor of CGRP, suppresses ERK phosphorylation and induces apoptosis, and reported on its potential therapeutic application to acute myeloid leukemia cells.

Free Research Field

敗血症

Academic Significance and Societal Importance of the Research Achievements

敗血症は感染に対する免疫反応の制御不全と定義され、急性の多臓器不全を引き起こす。毎年数百万人が罹患し、死亡のリスクも高い。DIC (Disseminated Intravascular Coagulation)は敗血症に効率に合併し、予後を著明に悪化させる。このため敗血症に引続くDICの病態解明と新規治療法的の開発は重要な課題である。本研究においては敗血症DICにおけるCGRPの役割の評価の過程でCGRP阻害薬のERKシグナルへの阻害効果を発見し急性骨髄性白血病細胞に対する治療応用可能性に関する報告を行った。敗血症DICにおけるCGRPの病態への関与を引き続き検討する予定としている。