The mechanism of inflammasome activation associated chronic inflammation on CKD.

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19501
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Kawasaki Medical School
• Principal Investigator: Nagasu Hajime 川崎医科大学, 医学部, 講師 (40412176)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 腎臓病 / 慢性炎症

Outline of Final Research Achievements

Chronic inflammation can be a major driver of the failure of a variety of organs, including chronic kidney disease (CKD). TNuclear factor erythroid2-related factor 2 (Nrf2), the master transcription factor for anti-oxidant responses, has also been implicated in inflammasome activation under physiological conditions. However, the mechanism underlying inflammasome activation in CKD remains elusive. Here, we show that the loss of Nrf2 suppresses inflammation in a unilateral ureter obstruction (UUO) model of CKD in mice. We consistently observed decreased expression of inflammation-related genes NLRP3 and IL-1β in Nrf2-deficient kidneys after UUO. Increased infiltration of M1, but not M2, macrophages appears to mediate the suppression of UUO-induced CKD symptoms. These results demonstrate that Nrf2-related inflammasome activation can promote CKD symptoms via infiltration of M1 macrophages. Thus, we have identified the Nrf2 pathway as a promising therapeutic target for CKD.

Free Research Field

腎疾患、炎症性疾患