Functional analysis for apical transporters by gene silencing in isolated and cultured renal proximal tubules.

• Project/Area Number: 15K19441
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Nakamura Motonobu 東京大学, 医学部附属病院, 助教 (40459524)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 水・電解質代謝学 / ナトリウム－プロトン交換輸送体 / ＮＨＥ / 腎臓内科学 / 水電解質代謝学 / ナトリウム輸送 / エンドサイトーシス / NHE活性 / V-ATPase活性 / 近位尿細管

Outline of Final Research Achievements

We aimed to explore the detailed mechanisms of sodium dependent acid base transport in the apical side of renal proximal tubules (PTs). Cell pH measurement was performed in freshly isolated PTs with several inhibitors including EIPA and DIDS, or in cultured PTs which was gene silenced with siRNA. Consequently, we revealed the existence of DIDS-sensitive components other than Na/H exchanger 3 in the apical side of PTs, which was a possible key in species differences of sodium dependent acid base transport among mice, rats and humans.

Research Products

• [Int'l Joint Research] Shin Kong Wu Ho-Su Memorial Hospital/National Defense Medical Center/Tri-Service General Hospital(Taiwan)
• [Int'l Joint Research] Providence St Vincent Medical Center(米国)
• [Journal Article] The role of renal proximal tubule transport in the regulation of blood pressure (2017)
  • Author(s): Shoko Horita1, Motonobu Nakamura, Masashi Suzuki, Nobuhiko Satoh, Atsushi Suzuki, Yukio Homma, Masaomi Nangaku
  • Journal Title: Kidney Research and Clinical Practice Volume: 36 Issue: 1 Pages: 12-21
  • DOI: 10.23876/j.krcp.2017.36.1.12
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Functional coupling of V-ATPase and CLC-5. (2017)
  • Author(s): Satoh N, Suzuki M, Nakamura M, Suzuki A, Horita S, Seki G, Moriya .
  • Journal Title: World Journal of Nephrology Volume: 6 Issue: 1 Pages: 14-20
  • DOI: 10.5527/wjn.v6.i1.14
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A pure chloride channel mutant of CLC-5 causes Dent’s disease via insufficient V-ATPase activation (2016)
  • Author(s): Nobuhiko Satoh, Hideomi Yamada, Osamu Yamazaki, Masashi Suzuki, Motonobu Nakamura, Atsushi Suzuki, Akira Ashida, Daisuke Yamamoto, Yoshitsugu Kaku, Takashi Sekine, George Seki, Shoko Horita
  • Journal Title: Pfluegers Aｒch Volume: 印刷中 Issue: 7 Pages: 1183-96
  • DOI: 10.1007/s00424-016-1808-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Selective insulin resistance in the kidney (2016)
  • Author(s): Shoko Horita, Motonobu Nakamura, Masashi Suzuki, Nobuhiko Satoh, Atsushi Suzuki, and George Seki
  • Journal Title: Biomed reserch international Volume: 印刷中
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport. (2015)
  • Author(s): Satoh N, Nakamura M, Suzuki M, Suzuki A, Seki G, Horita S.
  • Journal Title: Biomed Res Int Volume: 2015 Pages: 1-8
  • DOI: 10.1155/2015/971697
  • Peer Reviewed / Open Access
• [Journal Article] Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention. (2015)
  • Author(s): Horita S, Nakamura M, Satoh N, Suzuki M, Seki G.
  • Journal Title: PPAR Res Volume: 2015 Pages: 1-7
  • DOI: 10.1155/2015/646423
  • Peer Reviewed / Open Access
• [Journal Article] Species differences in regulation of renal proximal tubule transport by certain molecules (2015)
  • Author(s): Seki G, Nakamura M, Suzuki M, Satoh S, Horita S
  • Journal Title: World Journal of Nephrology Volume: 4 Issue: 2 Pages: 307-312
  • DOI: 10.5527/wjn.v4.i2.307
  • Peer Reviewed / Open Access
• [Journal Article] Stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in type 2 diabetes with nephropathy. (2015)
  • Author(s): Motonobu Nakamura; Nobuhiko Satoh; Masashi Suzuki; Haruki Kume; Yukio Homma; George Seki; Shoko Horita
  • Journal Title: Biochemical and Biophysical Research Communications Volume: in press Issue: 1 Pages: 154-8
  • DOI: 10.1016/j.bbrc.2015.04.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Therapeutic effect of prenatal alkalization and PTC124 in Na(+)/HCO3(-) cotransporter 1 p.W516* knock-in mice. (2015)
  • Author(s): Fang YW, Yang SS, Chau T, Nakamura M, Yamazaki O, Seki G, Yamada H, Hsu HM, Cheng CJ, Lin SH.
  • Journal Title: Gene Ther Volume: 22 Issue: 5 Pages: 374-81
  • DOI: 10.1038/gt.2015.7
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 近位尿細管管腔側Na依存性酸塩基輸送体の検討 (2017)
  • Author(s): 鈴木 淳司、鈴木 正志、中村 元信、佐藤 信彦、関 常司、佐藤 悠佑、本間 之夫、堀田 晶子、南学 正臣
  • Organizer: 第60回日本腎臓学会学術総会
  • Place of Presentation: 仙台
  • Year and Date: 2017-05-26
• [Presentation] 近位尿細管ナトリウム輸送調節におけるWNK1/OSR1/SPAKの意義 (2017)
  • Author(s): 中村 元信、鈴木 正志、佐藤 信彦、鈴木 淳司、塚田 弘之、関 常司、佐藤 悠佑、本間 之夫、堀田 晶子、南学 正臣
  • Organizer: 第60回日本腎臓学会学術総会
  • Place of Presentation: 仙台
  • Year and Date: 2017-05-26
• [Presentation] インスリンはIRS1/Akt2/mTORCを介して近位尿細管糖新生を抑制する。 (2017)
  • Author(s): 中村 元信、鈴木 正志、佐藤 信彦、鈴木 淳司、塚田 弘之、関 常司、佐藤 悠佑、本間 之夫、堀田 晶子、南学 正臣
  • Organizer: 第60回日本腎臓学会学術総会
  • Place of Presentation: 仙台
  • Year and Date: 2017-05-26
• [Presentation] インスリンによる近位尿細管Na再吸収亢進作用はAkt2とmTORC2を介している (2016)
  • Author(s): 中村元信、、鈴木正志、佐藤信彦、鈴木淳司、関常司、久米春喜、本間之夫、堀田晶子、南学正臣
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県 横浜市）
  • Year and Date: 2016-06-18
• [Presentation] 近位尿細管管腔側Na依存性酸塩基輸送機構の種差 (2016)
  • Author(s): 鈴木 淳司,鈴木 正志、中村 元信、佐藤 信彦、関 常司、久米 春喜、本間 之夫、堀田 晶子、南学 正臣
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-17
• [Presentation] インスリンによる近位尿細管Na再吸収亢進作用はAkt2とmTORC2を介している (2016)
  • Author(s): 中村 元信、鈴木 正志、佐藤 信彦、鈴木 淳司、関 常司、久米 春喜、本間 之夫、堀田 晶子、南学 正臣
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-17
• [Presentation] 近位尿細管管腔側Na依存性酸塩基輸送機構の種差 (2016)
  • Author(s): 鈴木淳司、鈴木正志、中村元信、佐藤信彦、関常司、久米春喜、本間之夫、堀田晶子、南学正臣
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県 横浜市）
  • Year and Date: 2016-06-17
• [Presentation] Regulation of blood pressure by renal proximal tubule transport (2016)
  • Author(s): Shoko Horita, Motonobu Nakamura, Masashi Suzuki, Nobuhiko Satoh, Atsushi Suzuki, Yukio Homma and Masaomi Nangaku
  • Organizer: The 36th Annual Meeting of the Korean Society of Nephrology
  • Place of Presentation: ソウル（大韓民国）
  • Year and Date: 2016-06-03
  • Int'l Joint Research / Invited
• [Presentation] 糖脂質代謝において近位尿細管のインスリン受容体基質が果たす役割の検討 (2015)
  • Author(s): 佐々木 元大, 窪田 直人, 笹子 敬洋, 熊谷 勝義, 石本 遊, 中村 元信, 稲城 玲子, 関 常司, 南学 正臣, 門脇 孝
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県 名古屋市）
  • Year and Date: 2015-06-05
• [Presentation] 微小灌流法を用いない単離近位尿細管管腔側輸送体機能の新規解析法 (2015)
  • Author(s): 佐藤 信彦, 中村 元信, 鈴木 正志, 堀田 晶子, 関 常司
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県 名古屋市）
  • Year and Date: 2015-06-05
• [Presentation] インスリンの近位尿細管Na輸送亢進作用は進行した糖尿病性腎症の高血圧維持に重要である (2015)
  • Author(s): 中村 元信, 堀田 晶子, 鈴木 正志, 佐藤 信彦, 榎本 裕, 久米 春喜, 本間 之夫, 関 常司
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県 名古屋市）
  • Year and Date: 2015-06-05