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ヒト腎臓におけるリン代謝機構を理解するためのオポッサム腎NaPi-IIc (Na+依存性Piトランスポーター)の解析
著者
藤井, 公 徳島大学大学院栄養生命科学教育部(人間栄養科学専攻)
Nishiguchi, Shiori University of Tokushima
Hanazaki, Ai University of Tokushima
Noguchi, Miwa University of Tokushima
Kirino, Ruri University of Tokushima
Sasaki, Sumire University of Tokushima
Tanifuji, Kazuya University of Tokushima
Koike, Megumi University of Tokushima
Yokoyama, Mizuki University of Tokushima
Arima, Yuki University of Tokushima
Ito, Mikiko University of Hyogo
キーワード
Phosphate
Transporter
Proximal tubule
Hereditary hypophosphatemic rickets with hypercalciuria
資料タイプ
学位論文
抄録
Background The role of Na+- dependent inorganic phosphate (Pi) transporters in the human kidney is not fully clarified. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is caused by loss-of-function mutations in the IIc Na+- dependent Pi transporter (NPT2c/Npt2c/NaPi-IIc) gene. Another Na+- dependent type II transporter, (NPT2A/Npt2a/NaPi-IIa), is also important for renal Pi reabsorption in humans. In mice, Npt2c deletion does not lead to hypophosphatemia and rickets because Npt2a compensates for the impaired Pi reabsorption. To clarify the differences between mouse and human, we investigated the relation between NaPi-IIa and NaPi-IIc functions in opossum kidney (OK) cells.
Methods We cloned NaPi-IIc from OK cells and created opossum NaPi-IIc (oNaPi-IIc) antibodies. We used oNaPi-IIc small interference (si)RNA and investigated the role of NaPi-IIc in Pi transport in OK cells.
Results We cloned opossum kidney NaPi-IIc cDNAs encoding 622 amino acid proteins (variant1) and examined their pH- and sodium-dependency. The antibodies reacted specifically with 75-kDa and 150-kDa protein bands, and the siRNA of NaPi-IIc markedly suppressed endogenous oNaPi-IIc in OK cells. Treatment with siRNA significantly suppressed the expression of NaPi-4 (NaPi-IIa) protein and mRNA. oNaPi-IIc siRNA also suppressed Na+/H+ exchanger regulatory factor 1 expression in OK cells.
Conclusion These findings suggest that NaPi-IIc is important for the expression of NaPi-IIa (NaPi-4) protein in OK cells. Suppression of Npt2c may downregulate Npt2a function in HHRH patients.
掲載誌名
Clinical and Experimental Nephrology
ISSN
13421751
14377799
cat書誌ID
AA11126935
出版者
Japanese Society of Nephrology|Springer
23
3
開始ページ
313
終了ページ
324
発行日
2018-10-13
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Toru Fujii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。
The final publication is available at Springer via https://doi.org/10.1007/s10157-018-1653-4
権利情報
© Japanese Society of Nephrology 2018
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
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3273号
学位記番号
甲栄第262号
学位授与年月日
2019-03-22
学位名
博士(栄養学)
学位授与機関
徳島大学
部局
医学系