ID | 113337 |
タイトル別表記 | ポドサイト傷害マウスモデルを用いた腎症進展に対する細胞外リン濃度の役割
Role of Extracellular Pi Levels on Kidney Disease Progression in a Podocyte Injury
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著者 |
前田, 彰
徳島大学大学院栄養生命科学教育部(人間栄養科学専攻)
Fukushima, Naoshi
Chugai Pharmaceutical Co., Ltd.
Horiba, Naoshi
Chugai Pharmaceutical Co., Ltd.
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キーワード | Focal segmental glomerulosclerosis
Kidney disease
Phosphate
Phosphate binder
Renal function
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資料タイプ |
学位論文
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抄録 | Background: Hyperphosphatemia is a major accelerator of complications in chronic kidney disease and dialysis, and phosphate (Pi) binders have been shown to regulate extracellular Pi levels. Research on hyperphosphatemia in mouse models is scarce, and few models display hyperphosphatemia induced by glomerular injury, despite its relevance to human glomerular disease conditions. In this study, we investigated the involvement of hyperphosphatemia in kidney disease progression using a mouse model in which hyperphosphatemia is induced by focal segmental glomerulosclerosis (FSGS). Methods: We established the NEP25 mouse model in which FSGS-hyperphosphatemia is induced by podocyte injury and evaluated the effect of a Pi binder, sevelamer. Results: After disease induction, we confirmed a gradual increase in serum Pi accompanied by reduced renal function and observed increases in serum FGF23 and PTH. Treatment with sevelamer significantly reduced serum Pi and urinary Pi fractional excretion and suppressed increases in serum FGF23 and PTH. A high dose improved serum creatinine and tubular injury markers, and pathological analysis confirmed amelioration of glomerular and tubular damage. Gene expression and marker analysis suggested protective effects on tubular epithelial cells in the diseased kidney. Compared to disease control, NEP25 mice treated with sevelamer retained their mRNA expression of Klotho, a known FGF23 co-receptor and renoprotective factor. Conclusions: Hyperphosphatemia caused by renal function decline was observed in a FSGS-induced NEP25 mouse model. Studies using this model showed that Pi regulation had a positive impact on kidney disease progression, and notably on tubular epithelial cell injury, which indicates the importance of Pi regulation in the treatment of kidney disease progression.
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掲載誌名 |
Nephron
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ISSN | 16608151
22353186
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cat書誌ID | AA1278405X
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出版者 | Karger
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巻 | 142
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号 | 2
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開始ページ | 135
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終了ページ | 146
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発行日 | 2019-02-07
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備考 | 内容要旨・審査要旨・論文本文の公開
本論文は,著者Akira Maedaの学位論文として提出され,学位審査・授与の対象となっている。 |
権利情報 | © 2019 S. Karger AG, Basel
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EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
博士論文全文を含む
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文科省報告番号 | 甲第3275号
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学位記番号 | 甲栄第264号
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学位授与年月日 | 2019-03-14
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学位名 |
博士(栄養学)
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学位授与機関 |
徳島大学
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部局 |
医学系
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