Elucidation of the mechanism of tissue remodeling exacerbated by endogenous AGEs and the development of novel targeted therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06657
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Shujitsu University
• Principal Investigator: MORI Shuji 就実大学, 薬学部, 教授 (50220009)
• Co-Investigator(Kenkyū-buntansha): 豊村 隆男 就実大学, 薬学部, 准教授 (40425137) ; 渡邊 政博 就実大学, 薬学部, 准教授 (10758246)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 炎症 / 組織リモデリング / サイトカイン

Outline of Final Research Achievements

We investigated the molecular identification of factors that interact with endogenous inflammatory factors (DAMPs and AGEs) related to the onset and exacerbation of tissue remodeling pathologies, and the regulatory mechanisms of inflammatory responses associated with the interactions (complex formation). We found that a cationic ribosomal protein (RPL9) exhibits high binding affinity to endogenous inflammatory factors and forms complexes with them via direct interactions. Furthermore, although RPL9 itself had no DAMPs activity, it significantly suppressed LPS+HMGB1 co-stimulation-induced enhancement of TNF-a expression and was found to have anti-DAMPs properties, suggesting a molecular understanding of tissue remodeling pathology and its potential as a new drug target.

Free Research Field

薬理学，応用薬理学

Academic Significance and Societal Importance of the Research Achievements

組織リモデリング病態の増悪化因子である内因性起炎因子（Damps，AGEs）による炎症の慢性化機序について解析し，新規結合因子（カチオン性RPs）の新規同定，複合体形成に伴う炎症応答の調節機構の存在を明らかにした。本知見は，炎症病態におけるDAMPs複合体形成に伴う新規の炎症応答制御機構の存在の可能性を示すものであると共に，組織リモデリング病態の分子理解と病態改善に向けた新規分子標的としての応用性を示唆するものである。