The regulation of autophagy and the development of polycystic kidneys by an intracellulat aquaporin

• Project/Area Number: 24591243
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Meiji Pharmaceutical University
• Principal Investigator: ISHIBASHI Kenichi 明治薬科大学, 薬学部, 教授 (80223022)
• Research Collaborator: TANAKA Yasuko 明治薬科大学, 病態生理学, 講師 (20386452)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 水チャネル / オートファジー / 腎のう胞 / 小胞体ストレス / 細胞内空胞 / 近位尿細管 / ノックアウトマウス / トランスジェニックマウス / アクアポリン / アポトーシス / 腎臓 / 脳 / 脈絡叢 / マイクロアレイ / 血管内皮細胞 / ＧＦＰ－ＬＣ３ / のう胞腎 / 脳浮腫 / ストップトフロー / 嚢胞腎 / 小胞体 / 血管内皮 / 脳梗塞

Outline of Final Research Achievements

The aquaporin-11 (AQP11) is a water channel expressed at the intracellular organelle. The AQP11 null mice are fatal due to kidney failure caused by polycystic kidneys around one month after birth. Before developing polycystic kidneys, their proximal tubular cells have multiple vesicles. We have identified enhanced autophagy, a self-degradative process in the proximal tubules of AQP11 null mice as well as their primary cultured cells with visualization of activated LC3, a marker for autophagy. Our results suggest that the manipulation of autophagy will be a promising treatment modality for polycystic kidneys.

Research Products

• [Journal Article] Aquaporin10 is a pseudogene in cattle and their relatives. (2015)
  • Author(s): Yasuko Tanaka, Yoshiyuki Morishita, Kenichi Ishibashi
  • Journal Title: Biochemistry and Biophysics Reports. Volume: 1 Pages: 16-21
  • DOI: 10.1016/j.bbrep.2015.03.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Delivery of microRNA-146a with polyethylenimine nanoparticle inhibits renal fibrosis in vivo (2015)
  • Author(s): Morishita Y, Imai T, Yoshizawa H, Watanabe M, Ishibashi K, Muto S, Nagata D.
  • Journal Title: International Journal of Nanomedicine Volume: 10 Pages: 3475-3488
  • DOI: 10.2147/ijn.s82587
  • Peer Reviewed / Open Access
• [Journal Article] Aberrant Glycosylation and Localization of Polycystin-1 Cause Polycystic Kidney in an AQP11 Knockout Model. (2014)
  • Author(s): Inoue Y, Sohara E, Kobayashi K, Chiga M, Rai T, Ishibashi K, Horie S, Su X, Zhou J, Sasaki S, Uchida S.
  • Journal Title: J Am Soc Nephrol. Volume: 25 Issue: 12 Pages: 2789-2799
  • DOI: 10.1681/asn.2013060614
  • Peer Reviewed
• [Journal Article] siRNAs targeted to Smad4 prevent renal fibrosis in vivo. (2014)
  • Author(s): Morishita Y, Yoshizawa H, Watanabe M, Ishibashi K, Muto S, Kusano E, Nagata D.
  • Journal Title: Sci Rep. Volume: 19 Issue: 1 Pages: 6424-6424
  • DOI: 10.1038/srep06424
  • Peer Reviewed / Open Access
• [Journal Article] The role of mammalian superaquaporins inside the cell (2014)
  • Author(s): Kenichi Ishibashi, Yasuko Tanaka, Yoshiyuki Morishita.
  • Journal Title: Biochimica et Biophysica Acta (BBA) - General Volume: 1840 Issue: 5 Pages: 1507-1512
  • DOI: 10.1016/j.bbagen.2013.10.039
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association of primary care physicians' exercise habits and their age, specialty, and workplace. (2013)
  • Author(s): Morishita Y, Numata A, Miki A, Okada M, Ishibashi K, Takemoto F, Ando Y, Muto S, Kusano E
  • Journal Title: J Multidiscip Healthc. Volume: 6 Pages: 409-414
  • DOI: 10.2147/jmdh.s52262
  • Peer Reviewed
• [Journal Article] Aliskiren suppresses the renin-angiotensin-aldosterone system and reduces blood pressure and albuminuria in elderly chronic kidney disease patients with hypertension. (2012)
  • Author(s): Morishita Ya, Yasui Ta, Numata Aa, Onishi Aa, Ishibashi K, Kusano E
  • Journal Title: Int J Nephrol Renovasc Dis. Volume: 5 Pages: 125-132
  • DOI: 10.2147/ijnrd.s36451
  • Peer Reviewed
• [Journal Article] Long-term effects of aliskiren on blood pressure and the renin-angiotensin-aldosterone system in hypertensive hemodialysis patients. (2012)
  • Author(s): Morishita Ya, Watanabe Ma, Hanawa Sa, Iimura Oa, Tsunematsu Sa, Ishibashi K, Kusano E
  • Journal Title: Int J Nephrol Renovasc Dis. Volume: 5 Pages: 45-51
  • DOI: 10.2147/ijnrd.s30203
  • Peer Reviewed
• [Presentation] 多発性嚢胞腎に進行するAQP11欠損マウスの腎組織におけるオートファジーおよびアポトーシス亢進 (2015)
  • Author(s): 田中靖子、渡真弓、石橋賢一
  • Organizer: 第135年会日本薬学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] サンドイッチELISA法による尿中エキソゾームの水チャネルAQP2の測定と尿浸透圧との相関 (2015)
  • Author(s): 滝沢凌健、新井健太、小沢遼平、武藤史彬、須藤直人、佐々木成、田中靖子、石橋賢一
  • Organizer: 第135年会日本薬学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] Enhanced Autophagy in the Proximal Tubule with Intracellular Vacuoles from AQP11 Null Mice Leading to the Development of Polycystic Kidneys (2014)
  • Author(s): Tanaka Y, Watari M, Takagi E, Sakamoto Y, Morishita Y, Ishibashi K.
  • Organizer: Renal Week 2014, American Society of Nephrology
  • Place of Presentation: Philadelphia, USA：convention center
  • Year and Date: 2014-11-13 – 2014-11-16
• [Presentation] Elongated Ciliary Length of Proximal Tubules in a PKD Model AQP11 Knockout Mouse (2014)
  • Author(s): Inoue Y, Sohara E, Kobayashi K, Rai T, Ishibashi K, Horie S, Su X, Zhou J, Sasaki S, Uchida S
  • Organizer: Renal Week 2014, American Society of Nephrology
  • Place of Presentation: Philadelphia, USA：convention center
  • Year and Date: 2014-11-13 – 2014-11-16
• [Presentation] アクアポリンによる水輸送調節：細胞膜アクアポリンと細胞内膜アクアポリン: (2014)
  • Author(s): 石橋賢一
  • Organizer: 第42回磁気共鳴医学会大会
  • Place of Presentation: 京都：ホテルグランヴィア京都
  • Year and Date: 2014-09-18 – 2014-09-20
  • Invited
• [Presentation] 反芻偶蹄哺乳類アクアポリン10(AQP10)遺伝子の偽遺伝子化 (2014)
  • Author(s): 石橋賢一、狛諒哉、野崎憲真、田中靖子
  • Organizer: 第57回日本腎臓学会学術総会
  • Place of Presentation: 横浜パシフィコ
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] シンポジウムS03「アクアポリンを標的とした診断・創薬の新たな可能性」ＡＱＰ欠損からみたＡＱＰの役割：AQP11と多発性のう胞腎 (2014)
  • Author(s): 石橋賢一
  • Organizer: 第１３４回日本薬学会年会
  • Place of Presentation: 熊本
  • Invited
• [Presentation] 細胞内水チャネルAQP11のマウス腎組織におけるオートファジー制御機構の解明 (2014)
  • Author(s): 田中靖子、高木瑛美、坂元雄基、倉光優太、清治めぐみ、石橋賢一
  • Organizer: 第１３４回日本薬学会年会
  • Place of Presentation: 熊本
• [Presentation] Aquaporin-10 May Not Be Physiologically Important in Mammals as Some Are Pseudogenes (2013)
  • Author(s): Kenichi Ishibashi, Ryouya Koma, Kenma Nozaki, Yasuko Tanaka, Yoshiyuki Morishita,
  • Organizer: Renal Week 2013, American Society of Nephrology
  • Place of Presentation: Atlanta, USA
• [Presentation] Aberrant Glycosylation and Localization of Polycystin-1 Cause Polycystic Kidney in AQP11-Knockout Mice (2013)
  • Author(s): Yuichi Inoue, Eisei Sohara, Katsuki Kobayashi, Tatemitsu Rai, Kenichi Ishibashi, Shigeo Horie, Xuefeng Su, Jing Zhou, Sei Sasaki, Shinichi Uchida,
  • Organizer: Renal Week 2013, American Society of Nephrology
  • Place of Presentation: Atlanta, USA
• [Presentation] AQP11欠損による多発性嚢胞腎発症に関与する遺伝子とタンパクの網羅的解析 (2013)
  • Author(s): 石橋賢一、近藤信太郎、山本格、田中靖子
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京
• [Presentation] 脳浮腫治療をめざした脳梗塞モデルマウスにおけるアクアポリン１１の機能解析 (2013)
  • Author(s): 田中靖子、一柳美聡、倉光優太、清治めぐみ、山本龍世、石橋賢一
  • Organizer: 日本薬学会１３３年会
  • Place of Presentation: 横浜
• [Presentation] 近位尿細管起源の多発性のう胞腎モデル（AQP11欠損マウス）の経時摘アレイ解析 (2013)
  • Author(s): 近藤信太郎、田中靖子、山本格、石橋賢一
  • Organizer: 日本薬学会１３３年会
  • Place of Presentation: 横浜
• [Presentation] 水チャネルAQP11の血清浸透圧による脳と腎臓における発現動態 (2012)
  • Author(s): 石橋賢一、山岸いずみ、青野遥香、石澤真依子、田中靖子
  • Organizer: 第55回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] ER-Stress and Endosomal Abnormalities in the Kidney of AQP11 Null Mice (2012)
  • Author(s): Shintaro Kondo, Tadashi Yamamoto,, Yasuko Tanaka, Kenichi Ishibashi
  • Organizer: Renal Week 2012, American Society of Nephrology,
  • Place of Presentation: San Diego, USA
• [Presentation] Impaired Trafficking of Polycystin-1 May Be a Key Mechanism of Cyst Formation in the Aquaporin-11 Knockout Mouse (2012)
  • Author(s): Yuichi Inoue, Eisei Sohara, Katsuki Kobayashi, Tatemitsu Rai, Kenichi Ishibashi, Sei Sasaki, Shinichi Uchida
  • Organizer: Renal Week 2012, American Society of Nephrology,
  • Place of Presentation: San Diego, USA
• [Book] Navigate 呼吸器疾患 (2015)
  • Author(s): 石橋賢一
  • Publisher: 医学書院
• [Book] Navigate 循環器疾患 (2014)
  • Author(s): 石橋賢一
  • Total Pages: 314
  • Publisher: 医学書院
• [Book] Navigate 神経疾患 (2013)
  • Author(s): 石橋賢一
  • Total Pages: 287
  • Publisher: 医学書院
• [Book] Navigate 腎疾患 (2013)
  • Author(s): 石橋賢一
  • Total Pages: 209
  • Publisher: 医学書院
• [Remarks] ようこそ明治薬科大学・病態生理学教室へ
  • URL: http://www.my-pharm.ac.jp/~kishiba/sub5.html
• [Remarks] 研究テーマ（病態生理学教室）
  • URL: http://www.my-pharm.ac.jp/~kishiba/sub3.html