Role of the prostanoid in cisplatin-induced nephropathy

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790246
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Kitasato University (2014); Asahikawa Medical College (2012-2013)
• Principal Investigator: KOJIMA Fumiaki 北里大学, 医療衛生学部, 准教授 (30550545)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: プロスタノイド

Outline of Final Research Achievements

We investigated the role of the EP1 receptor (a prostaglandin (PG) E2 receptor subtype) in the cisplatin-induced acute kidney injury using EP1 knock-out (KO) mice. Three days following cisplatin injection, nephrotoxicity biomarkers including plasma creatinine, blood urea nitrogen (BUN) and kidney injury molecule-1 (Kim-1) were significantly increased in wild-type (WT) mice, while these changes were diminished in EP1 KO mice. Histopathological analyses further showed a significant reduction in structural damages in EP1 KO kidney compared to WT kidney after cisplatin injection. In addition, the improvements of functional and structural abnormalities consistent with nephrotoxicity observed in EP1 KO mice were associated with significantly lower levels of renal inflammatory cytokine expression and oxidative stress. These results indicate that PGE2-EP1 system plays a crucial role in cisplatin-induced nephrotoxicity.

Free Research Field

薬理学