Mechanism of Acute Kidney Injury Induced by Remote organ injury

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21319
• Project/Area Number (Other): 18H06216 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Jichi Medical University
• Principal Investigator: Komada Takanori 自治医科大学, 医学部, 助教 (90824730)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: インフラマソーム / Absent in melanoma 2 / 二本鎖DNA

Outline of Final Research Achievements

Acute kidney injury (AKI) is known worsened under conditions of multi-organ or remote-organ failure. In this study, we examined the hypothesis that dead cell DNA derived from rhabdomyolysis reaches the kidney and influences the AKI onset through a DNA sensor, absent in melanoma 2 (AIM2). Using a rhabdomyolysis-induced AKI (RIAKI) model, we compared the pathophysiological changes under RIAKI between AIM2 knockout and wild-type mice. Dead cell DNA was involved in AKI progression, but AIM2 deficiency worsened AKI. Our results indicated that AIM2 contributed to AKI independently of the inflammasome.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

横紋筋融解症による急性腎障害は、特異的な治療法がなく腎予後・生命予後に影響する。本研究では、壊死細胞二本鎖DNAが治療標的となりうること、また細胞質内DNAセンサーであるAIM2が病態に関与することを示した。今後詳細にその機序をあきらかにすることで、AKIの新たな治療法開発に繋がることが期待できる。