2021 Fiscal Year Final Research Report
Development of the prediction system for tubular secretion of drugs in the human kidney
Project/Area Number |
18K06766
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47060:Clinical pharmacy-related
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Research Institution | Ritsumeikan University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2022-03-31
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Keywords | 薬物トランスポーター / 尿細管分泌 / 経細胞輸送 / 薬物相互作用 / 培養細胞 |
Outline of Final Research Achievements |
At present, it is difficult to accurately predict the degree of tubular secretion involved in renal excretion of drugs and the contribution of drug transporters involved in tubular secretion. In this study, we examined the effect of expression of transcription factors involved in the regulation of drug transporter expression on the expression of drug transporters in human kidney-derived HK-2 cells. It was demonstrated that HK-2 cells stably expressing HNF1α showed a increased expression of megalin, which is responsible for endocytosis of low molecular weight proteins and drugs. The nephrotoxicity of aminoglycoside antibiotics, substrates of megalin, is significantly enhanced in HK-2 cells stably expressing HNF1α.
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Free Research Field |
薬物動態学
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Academic Significance and Societal Importance of the Research Achievements |
本研究は、薬物の腎移行動態を評価しうる評価系の構築を目指したものであり、ヒト腎由来HK-2細胞においてHNF1αを発現させることにより、メガリンの発現が上昇することを明らかにした。メガリンを恒常的に発現するヒト由来培養腎上皮細胞は存在しないことから、HNF1α安定発現HK-2細胞は、メガリンの機能評価やアミノグリコシド系抗生物質の腎毒性評価が可能なin vitro実験系となりうることが示唆され、今後の新薬開発においても有用な評価系となることが期待される。
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