Role of antioxidant and DNA-repair enzyme apurinic/apyrimidinic endonuclease 1 in kidney injury

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15992
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Asahikawa Medical College
• Principal Investigator: Maruyama Keisuke 旭川医科大学, 大学病院, 客員助教 (30648324)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: APE1 / 慢性腎臓病 / 抗酸化ストレス

Outline of Final Research Achievements

Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein that controls the cellular response to oxidative stress and possesses DNA-repair functions. Its function and therapeutic prospects with respect to kidney injury are unknown. To study this, we activated APE1 during kidney injury by constructing an expression vector (pCAG-APE1), using an EGFP expression plasmid (pCAG-EGFP) as a control. We performed unilateral ureteral obstruction (UUO) as a model of tubulointerstitial fibrosis on ICR mice before each vector was administrated via retrograde renal vein injection. In this model, pCAG-APE1 injection significantly reduced histological end points including fibrosis, inflammation, tubular injury, and oxidative stress. qPCR analysis showed significantly lower expression of Casp3 and inflammation-related genes in pCAG-APE1-injected animals . Thus, therapeutic APE1 modulation might be beneficial for the treatment of renal diseases.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

我々は抗酸化ストレス酵素APE1の尿管結紮モデルでの腎間質線維化における役割とその作用機構を解明した。APE1は酸化ストレスの軽減のみならず、免疫機能を調整することで腎保護的に作用することを明らかにした。これらの結果より、APE1の慢性腎臓病に対する新しい治療法としての可能性が強く示唆された。