Differential roles of RAGE species for renal tubular damages

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K23941
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Miyagawa Taro 金沢大学, 附属病院, 特任助教 (20738207)
• Project Period (FY): 2019-08-30 – 2022-03-31
• Keywords: 急性腎障害 / RAGE / sRAGE / HMGB1

Outline of Final Research Achievements

Acute kidney injury (AKI) is an important risk factor for the development of chronic kidney disease and end-stage renal failure. This study focused on soluble RAGE (sRAGE) and investigated the protective mechanism of sRAGE against AKI. In an ischemia-reperfusion model of AKI, RAGE deficiency exacerbated AKI.
In proximal tubular cells exposed to hypoxia, inflammatory cytokines including high mobility group box 1 (HMGB1) were decreased and cell proliferative capacity was improved in the presence of sRAGE.
In an AKI model, sRAGE treatment reduced AKI. These results suggest that sRAGE may be protective in ischemia-reperfusion-induced AKI.

Free Research Field

腎臓学

Academic Significance and Societal Importance of the Research Achievements

虚血再灌流による尿細管障害を背景としたAKIにおいて、デコイ型受容体であるsRAGEの存在が重要な機能を担い、HMGB1がsRAGEに捕捉され、腎障害が軽減する可能性があることが初めて明らかとなった。さらに、リコンビナントsRAGEの投与により、HMGB1の炎症性シグナルが抑制され、腎障害に対し保護的に働くことも分かった。以上より、RAGE/sRAGEを介したAKI発症の分子機序が明らかになるとともに、sRAGE補充療法がAKIの新規治療法として有用である可能性が示された。