Involvement of OATP4C1 in the development of methotrexate-induced lung injury

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K21371
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology; Respiratory organ internal medicine
• Research Institution: Showa University
• Principal Investigator: OHBAYASHI MASAYUKI 昭和大学, 薬学部, 講師 (70349041)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 薬剤性肺障害 / OATP4C1 / 肺胞上皮細胞 / EMT / 薬物トランスポーター

Outline of Final Research Achievements

In this study, we focused on drug-induced lung injury caused by methotrexate (MTX), a drug for rheumatoid arthritis that has been used in clinical practice and has reported adverse effects on lung injury. It was shown that OATP4C1, which is responsible for MTX transport, is expressed in alveolar epithelial cells and contributes to MTX-mediated cell injury. Moreover, it was shown that accumulation of MTX cells via OATP4C1 promotes EMT such as cell shape change and acquisition of migration ability. It was suggested that OATP4C1 expressed in alveolar epithelial cells of patients with MTX-induced lung injury may contribute to the onset of lung injury.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

肺胞上皮細胞に発現するOATP4C1が輸送を担う医薬品による薬剤性肺障害発症機序の解明につながり、将来、OATP4C1の薬剤性肺障害の新たな治療方法の開発や副作用を予測するバイオマーカーとなりうつ可能性を秘めていることが特色である。