To elucidate the mechanism of anti inflammatory effect by activation of the aryl hydrocarbon receptor pathway in tubulointerstitium

• Project/Area Number: 18K15972
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: University of Yamanashi
• Principal Investigator: TAKAMURA TAKEYUKI 山梨大学, 大学院総合研究部, 医学研究員 (30814248)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: AhR / 芳香族炭化水素受容体 / 尿細管間質 / 慢性腎臓病 / 尿細管上皮細胞

Outline of Final Research Achievements

There are 13 million chronic kidney disease (CKD) patients and ten thousand of them are required to start dialysis treatment every year in Japan. There is a need to develop curative treatments of CKD. This study investigated whether the activation of the AhR pathway affects CKD. Our experimental results suggested that the activation of the AhR pathway may induce the mRNA expression of CYP1A1, a major target gene of the AhR/xenobiotic responsive element pathway, increased in the kidney of the mice.

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病患者は約1300万人といわれ、今や腎臓病は国民病と考えられているものの腎不全の根治療法は存在せず、腎移植もドナー不足に悩まされているのが現状であり、腎機能低下の治療や進展予防に期待する社会的要望は強い。これまで明らかとなっていない、芳香族炭化水素受容体(AhR)の活性化が尿細管間質における炎症抑制に寄与している可能性があることは、新規治療法の開発につながる意義を持つと考えられる。