Study of the pathophysiological significance of endogenous AGE as an exacerbating factor for tissue remodeling, and the development of novel targeted therapy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06807
• 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, 講師 (40425137) ; 渡邊 政博 就実大学, 薬学部, 講師 (10758246)
• Project Period (FY): 2018-04-01 – 2021-03-31
• 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 identification of novel binding factors for Damps or AGEs molecules with the pattern recognition receptors-stimulating activity, the formation of inflammatory complex and their pathophysiological significance. The chromatographic analysis using AGEs-immobilized affinity gel revealed the existence of some binding factors. Recombinant binding factor was shown to affect the damps-induced inflammatory response in macrophage cells. This finding suggests that there is the control mechanism by the complex formation with damps, suggesting the further understanding of tissue remodeling associated with chronic inflammation and its applicability as new drug discovery target.

Free Research Field

薬理学，応用薬理学

Academic Significance and Societal Importance of the Research Achievements

生活習慣病の増悪化因子としてDampsやAGEs分子による過剰な免疫応答に焦点をあて，それらの生体内活性制御機構の解析研究を実施した。特に，結合因子の同定，起炎性複合体の形成に着目して研究を進めたところ，複数個の結合因子の存在が明らかとなり，これらの結合因子はDamps刺激による炎症応答に対して有意に影響を与えることが明らかとなった。本知見は，Damps複合体形成に伴う炎症応答制御機構の存在の可能性を拓くとともに，組織リモデリング病態の分子理解と新たな治療標的としての応用性を示唆するものである。