2018 Fiscal Year Final Research Report
Elucidation of the function of glycosylation enzyme OGT in the renal tubule using tissue specific knockout mouse
Project/Area Number |
17K16094
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Kidney internal medicine
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Research Institution | Keio University |
Principal Investigator |
Minami Yukiko 慶應義塾大学, 医学部(信濃町), 助教 (30793880)
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Project Period (FY) |
2017-04-01 – 2019-03-31
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Keywords | ミネラルコルチコイド受容体(MR) / O-GlcNAcトランスフェラーゼ(OGT) / 糖鎖修飾 |
Outline of Final Research Achievements |
O-GlcNAc transferase (OGT) is ubiquitously expressed but the study for tissue specific role of OGT has been limited. In this study, renal tubule-specific OGT knockout (KO) mice were established and analyzed. In vitro assay demonstrated that OGT interacts with mineralocorticoid receptor (MR) as a coactivator and this KO model exhibited severe dehydration and decreased expression of MR-target gene such as epithelial sodium channel (ENaC), which is consistent with the result of in vitro study. In addition, this KO model exhibited impaired function and abnormal morphology in the kidney, suggesting that renal tubule OGT also has protective role on kidney development.
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Free Research Field |
内分泌学
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Academic Significance and Societal Importance of the Research Achievements |
これまでの報告で、全身OGT ノックアウトマウスモデルは胎生致死であり、また誘導型心筋特異的OGT ノックアウトマウスを用いた検討では、OGTは心筋に対し保護的な機能を有することが明らかになっていたが、他臓器におけるOGTの機能については未解明な点が多かった。本研究成果から、OGTの腎尿細管特異的な機能について新たな知見が得られたことは、学術的に重要な意義を持つ。OGTを介して行われる糖鎖修飾は、糖尿病など生活習慣病の病態形成にも深く関与する。本研究成果を通じて得られた腎尿細管OGT機能に関する知見は、糖尿病や腎不全の新たな治療戦略への糸口になることが期待される。
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