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Translational control of urate transporters via microRNAs

37 months
Approved budget:
Dr Andrew Bahn
Health issue:
Renal and urogenital
Proposal type:
Emerging Researcher First Grant
Lay summary
Urate, the end product of purine metabolism in humans, may cause gout and has a significant impact on cardiovascular as well as neurodegenerative diseases. Recently, important urate transporters (OAT4, URAT1, ABCG2 and GLUT9) were identified to control urate plasma levels. The objective of this study is to explore how the amounts of the urate transporter protein GLUT9 are altered by microRNAs, which change the process of GLUT9 mRNA translation. Luciferase assays on GLUT9 DNA constructs will be performed to define important sequences for its translational regulation. Moreover, the influence of commonly used drugs such as diuretics, and urate itself, on the microRNA profile and consequently on GLUT9 expression will be examined. These studies will extend our understanding of renal urate handling and the influence of drugs on the development of gout, which is a major problem in the Maori population, and other diseases such as metabolic syndrome and diabetes type II.