Effects of DNA Aptamer Raised Against RAGE on Sepsis in Mice

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09086
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kurume University
• Principal Investigator: Koga Yoshinori 久留米大学, 医学部, 助教 (70569433)
• Co-Investigator(Kenkyū-buntansha): 松井 孝憲 久留米大学, 医学部, 准教授 (10425233)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: RAGE / 核酸医薬 / RAGEアプタマー / 敗血症

Outline of Final Research Achievements

In this study, we examined whether and how RAGE-aptamer could improve survival rate and organ damage in LPS-injected septic mice.
RAGE-aptamer significantly improved sepsis score at 8 hours after LPS injection and survival rate at 24 hours (70%) in septic mice compared with LPS+vehicle- or LPS+control-aptamer-treated mice. RAGE-aptamer treatment significantly decreased the expression of p-NF-κB p65, an active form of redox-sensitive transcriptional factor, NF-κB, and gene or protein expression of TNF-α, IL-1β, IL-6, and HMGB1 in serum, peripheral monocytes, and kidneys of septic mice in association with the reduction of oxidative stress and improvement of metabolic acidosis, renal and liver damage.
Our present study suggests that RAGE-aptamer could attenuate multiple organ damage in LPS-injected septic mice partly by inhibiting the inflammatory reactions via suppression of HMGB1-RAGE interaction.

Free Research Field

外科学

Academic Significance and Societal Importance of the Research Achievements

RAGEに結合する炎症性リガンドを、核酸医薬：RAGEアプタマーを用いてその結合を阻害することで、敗血症モデル動物の死亡率が抑えられることを明らかにした。敗血症により世界中で年間500万人以上が死亡していると推定されているが、有効性の高い治療法はまだ確立していない。今回の研究成果により、RAGEを標的とした重症感染症による敗血症に対して、RAGEアプタマーが新しい治療手段になる可能性を示唆することが出来た。