Elucidation of the mechanism of NLRP3 inflammasome regulation by ARIH2

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17536
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Jichi Medical University
• Principal Investigator: Kamata Ryo 自治医科大学, 医学部, 客員研究員 (60801420)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: インフラマソーム / ユビキチン / ARIH2

Outline of Final Research Achievements

Sterile inflammation is known to be involved in the development of vascular diseases such as atherosclerosis and aneurysms. The NLRP3 inflammasome, an intracellular protein complex, has been focused on as one of the pathways to induce sterile inflammation.
We have clarified the role of the NLRP3 inflammasome and its regulatory mechanism in various diseases.
In the present study, we found that the E3 ubiquitin ligase ARIH2, newly identified from the NLRP3 inflammasome complex, ubiquitinates NLRP3, and as a result, NLRP3 is degraded by the proteasome. Furthermore, by using macrophage-specific ARIH2-deficient mice (ARIH2flox/flox; CreLyzM), we found that ARIH2 negatively regulates the NLRP3 inflammasome in vivo.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、ARIH2はNLRP3の発現をユビキチン-プロテアソーム系によって制御し、炎症反応を制御していることを明らかにした。これまでに、NLRP3インフラマソームは様々な疾患の発症機構への関与が示されていることから、ARIH2によるNLRP3インフラマソームの制御機構の一端を明らかにしたことで、様々な疾患の病態解明や新たな治療方法の確立に大きく貢献することが期待できる。