Elucidation of the mechanism of gout attacks

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K15200
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Shinshu University
• Principal Investigator: Sawamura Tatsuya 信州大学, 学術研究院医学系, 教授 (30243033)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 痛風 / 尿酸結晶 / 受容体

Outline of Final Research Achievements

Acute gout attack is an arthritis accompanied with severe pain. The severe inflammation in the gout attack is though to be triggered by uric acid crystals. However, it is still unclear how the inflammation is triggered. In this study, we aimed to elucidate the mechanism of promoting inflammation by uric acid crystals and the pathophysiology of gout attack.
Here, we found receptor X recognizes uric acid crystals. We also found that receptor X functioned in macrophages and neutrophils to promote the inflammatory response triggered by uric acid crystals. Furthermore, receptor X-gene deletion alleviated the symptoms of uric acid crystal-induced mouse arthritis model. These data suggested the involvement of the receptor in the pathogenesis of gout attack.

Free Research Field

血管医学、薬理学

Academic Significance and Societal Importance of the Research Achievements

痛風は100万人近い患者が通院し、原因となる高尿酸血症も500万人以上の患者がいる疾患である。しかし、痛風への治療は、高尿酸血症を対象としたものが主体となり、痛風発作に関してはコルヒチンがヒポクラテス以来数千年間使用され続けている。本研究により、痛風発作のメカニズムが解明できれば、コルヒチン効果を説明するのみにならず、新規メカニズムに基づく痛風発作治療薬を創出できる可能性がある。