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Omics analysis applicable to preemptive medicine of chronic kidney disease -focusing on comprehensive analysis of phosphorylated proteins-

Research Project

Project/Area Number 15K08435
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionFujita Health University

Principal Investigator

Nagao Shizuko  藤田保健衛生大学, 研究支援推進センター疾患モデル教育研究施設, 教授 (20183527)

Co-Investigator(Kenkyū-buntansha) 吉原 大輔  藤田保健衛生大学, 大学共同利用機関等の部局等, 助教 (70454402)
釘田 雅則  藤田保健衛生大学, 大学共同利用機関等の部局等, 講師 (50440681)
Co-Investigator(Renkei-kenkyūsha) Yuzawa Yukio  藤田保健衛生大学, 医学部・腎内科学, 教授 (00191479)
Suzuki Atsushi  藤田保健衛生大学, 医学部・内分泌代謝内科学, 教授 (90340265)
Saito Kuniaki  藤田保健衛生大学, 医療科学部, 教授 (80262765)
Kurahashi Hiroki  藤田保健衛生大学, 総合医科学研究所・分子遺伝学, 教授 (30243215)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords慢性腎臓病 / メタボロミクス / プロテオミクス / リン酸化 / 多発性嚢胞腎 / 多発性嚢胞腎症 / メタボローム / 環境因子 / 塩分摂取 / オミックス解析 / りん酸化タンパク質 / 網羅的解析
Outline of Final Research Achievements

In order to clarify deteriorated factors of chronic kidney disease (CKD), kidneys of CKD animal model were analyzed by an omics approach. PCK rat is an animal model by orthogons Pkhd1 gene for human polycystic kidney disease. In PCK cystic kidney, the metabolites levels increased in TCA cycle, urea cycle, branched chain amino acid metabolism and nucleic acid metabolism, the metabolites levels also changed in lipid and sugar related metabolism. Pcy mouse is an animal model by orthogons Nphp3 gene for human nephronophthisis. The metabolites levels of nucleic acid, TCA cycle, urea cycle, aromatic amino acid and lipid metabolism changed in pcy cystic kidneys. 17 proteins in PCK rats and 35 proteins in pcy mice significantly changed by a comprehensive analysis of phosphorylated proteins. These results will be developed into researches contributing to human preemptive medicine of chronic kidney disease.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (28 results)

All 2018 2017 2016 2015 Other

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (21 results) (of which Int'l Joint Research: 10 results) Remarks (3 results)

  • [Journal Article] Mitochondrial Abnormality Facilitates Cyst Formation in Autosomal Dominant Polycystic Kidney Disease2017

    • Author(s)
      Ishimoto Y, Inagi R, Yoshihara D, Kugita M, Nagao S, Shimizu A, Takeda N, Wake M, Honda K, Zhou J, Nangaku M
    • Journal Title

      Mol Cell Biol

      Volume: e-Pub Issue: 24

    • DOI

      10.1128/mcb.00337-17

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct oxylipin alterations in diverse models of cystic kidney diseases.2017

    • Author(s)
      Md Monirujjamana, Jessay G. Devassy, Tamio Yamaguchi, Nikhil Sidhu, Masanori Kugita, Melissa Gabbs, Shizuko Nagao, Jing Zhou, Amir Ravandi, Harold M. Aukema.
    • Journal Title

      Biochim Biophys Acta. -Molecular and Cell Biology of Lipids-

      Volume: 1862(12) Issue: 12 Pages: 1562-1574

    • DOI

      10.1016/j.bbalip.2017.08.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Beneficial effect of combined treatment with octreotide and pasireotide in PCK rats, an orthologous model of human autosomal recessive polycystic kidney disease.2017

    • Author(s)
      Masanori Kugita, Kazuhiro Nishii, Tamio Yamaguchi, Atsushi Suzuki, Yukio Yuzawa, Shigeo Horie, Eiji Higashihara, Shizuko Nagao.
    • Journal Title

      PLoS One.

      Volume: 12(5) Issue: 5 Pages: e0177934-e0177934

    • DOI

      10.1371/journal.pone.0177934

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant Smad3 phosphoisoforms in cyst-lining epithelial cells in the cpk mouse, a model of autosomal recessive polycystic kidney disease2017

    • Author(s)
      Hama Taketsugu、Nakanishi Koichi、Sato Masashi、Mukaiyama Hironobu、Togawa Hiroko、Shima Yuko、Miyajima Masayasu、Nozu Kandai、Nagao Shizuko、Takahashi Hisahide、Sako Mayumi、Iijima Kazumoto、Yoshikawa Norishige、Suzuki Hiroyuki
    • Journal Title

      American Journal of Physiology-Renal Physiology

      Volume: 313 Issue: 6 Pages: F1223-F1231

    • DOI

      10.1152/ajprenal.00697.2016

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Role of Retinoid X receptor pathway in cystogenesis with therapeutic potential in polycystic kidney disease.2018

    • Author(s)
      Masanori Kugita, Tamio Yamaguchi, Harold M Aukema, Kazuhiro Nishii and Shizuko Nagao
    • Organizer
      ISN Frontiers Meetings 2018, Tokyo, JAPAN, 2018 Feb 22-25
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Renal and serum oxylipin alterations in the jck mouse, an orthologous model of human nephronophthisis.2018

    • Author(s)
      Tamio Yamaguchi, Md Monirujjaman, Jessay G. Devassy, Melissa Gabbs, Nikhil Sidhu, Arumi Jha, Andrew J. Halayko, Masanori Kugita, Shizuko Nagao, Amir Ravandi, Harold M. Aukema
    • Organizer
      ISN Frontiers Meetings 2018, Tokyo, JAPAN, 2018 Feb 22-25
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Suppressive Effect of RXR Ligand and MEK Inhibitor on RXR Expression and Cellular Proliferation in Immortalized Polycystic Kidney Cells.2017

    • Author(s)
      Masanori Kugita, Tamio Yamaguchi, Kazuhiro Nishii, Mai Sasaki, Noboru Ogiso, Harold M. Aukema, Shizuko Nagao
    • Organizer
      Kidney week 2017, New Orleans, LA, U.S.A., 2017 Oct 31-Nov 5
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Altered Liver Bioactive Lipid (Oxylipin) Profiles in PCK Rats with Polycystic Kidney and Liver Disease.2017

    • Author(s)
      Tamio Yamaguchi, Jessay G. Devassy, Aruni Jha, Andrew J Halayko, Masanori Kugita, Shizuko Nagao, Amir Ravandi, Harold M Aukema
    • Organizer
      Kidney week 2017, New Orleans, LA, U.S.A., 2017 Oct 31-Nov 5
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Kidney Glycosphingolipidomics and Metabolomics Reveal Metabolic Crosstalk between Elevated Glycosphingolipids and Glucose Metabolisms in PKD Progression.2017

    • Author(s)
      Kazuki Nakajima, Kazuo Takahashi, Masanori Kugita, Shizuko Nagao, Yukio Yuzawa
    • Organizer
      Kidney week 2017, LA, U.S.A., 2017 Oct 31-Nov 5
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アルツハイマー病治療に向けて-血液からのAβ除去による認知機能改善効果-2016

    • Author(s)
      川口 和紀、坂田 美和、酒井 一由、比企 能之、加藤 政雄、長尾 静子、 間宮 隆吉、鍋島 俊隆、北口 暢哉
    • Organizer
      第35回日本認知症学会学術集会
    • Place of Presentation
      東京 東京国際フォーラム
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report
  • [Presentation] 組織再生促進デバイス:細胞と天然高分子粉体との混合物による成長因子産生能の検討2016

    • Author(s)
      堀秀生、新里昌功、新美元、長尾静子、比企能之、北口暢哉
    • Organizer
      第54回日本人工臓器学会大会
    • Place of Presentation
      鳥取県 米子 米子コンベンションセンター(BIG SHIP)
    • Year and Date
      2016-11-23
    • Related Report
      2016 Research-status Report
  • [Presentation] Increased salt intakes dose not deteriorate renal cystic disease progression in high water loaded PCK rats.2016

    • Author(s)
      Masanori Kugita, Tamio Yamaguchi, Yoichi Nagamura, Harold M Aukema, Shizuko Nagao.
    • Organizer
      Kidney Week 2016
    • Place of Presentation
      Chicago, IL, U.S.A.
    • Year and Date
      2016-11-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Bioactive Lipid Alterations in the jck and pcy mouse models of nephronophthisis.2016

    • Author(s)
      Tamio Yamaguchi, Nikhil Sidhu, Jessay Gopuran Devassy, Melissa Gabbs, Amir Ravandi, Masanori Kugita, Shizuko Nagao, Harold M. Aukema.
    • Organizer
      Kidney Week 2016
    • Place of Presentation
      Chicago, IL, U.S.A.
    • Year and Date
      2016-11-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mitochondrial dysfunction contributes to cysts proliferation of autosomal dominant polycystic kidney disease.2016

    • Author(s)
      Yu Ishimoto, Masaomi Nangaku, Masanori Kugita, Shizuko Nagao, Akira Shimizu, Jing Zhou, Reiko Inagi.
    • Organizer
      Kidney Week 2016
    • Place of Presentation
      Chicago, IL, U.S.A.
    • Year and Date
      2016-11-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Differential expressions of miR-378a-3p/ADAMTS1 in cpk mice, a model of ARPKD2016

    • Author(s)
      Masashi Sato, Koichi Nakanishi, Taketsugu Hama, Hironobu Mukaiyama, Hiroko Togawa, Yuko Shima, Masayasu Miyajima, Kandai Nozu, Shizuko Nagao, Hisahide Takahashi, Kazumoto Iijima, Norishige Yoshikawa and Hiroyuki Suzuki.
    • Organizer
      Kidney Week 2016
    • Place of Presentation
      Chicago, IL, U.S.A.
    • Year and Date
      2016-11-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 血中アミロイドβ蛋白(Aβ)除去によるアルツハイマー病治療システム;ラット血中Aβ除去による血液・髄液中Aβの変化2016

    • Author(s)
      川口和紀、木野村淳、平林晃知、渡辺康太、青木洋樹、榊原由莉、坂田美和、釘田雅則、加藤政雄、長尾静子、北口暢哉
    • Organizer
      第6回日本認知症予防学会学術集会
    • Place of Presentation
      宮城県、仙台 東北大学百周年記念会館川内萩ホール
    • Year and Date
      2016-09-23
    • Related Report
      2016 Research-status Report
  • [Presentation] Mitochondrial dysfunction contributes to cyst proliferation of autosomal dominant polycystic kidney disease.2016

    • Author(s)
      Yu Ishimoto, Masaomi Nangaku, Shizuko Nagao, Daisuke Yoshihara, Masanori Kugita, Yoko Yoshida, Jing Zhou, Mike Murphy, Akira Shimizu, Reiko Inagi.
    • Organizer
      The Asian Pacific Society of Nephrology
    • Place of Presentation
      Perth, WA, Australia
    • Year and Date
      2016-09-17
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ミトコンドリア機能異常は多発性嚢胞腎の嚢胞形成に関与する2016

    • Author(s)
      石本遊、南学正臣、吉原大輔、釘田雅則、長尾静子
    • Organizer
      第59回日本腎臓学会学術総会
    • Place of Presentation
      神奈川県、横浜 パシフィコ横浜
    • Year and Date
      2016-06-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 多発性嚢胞腎症モデル動物の腎臓におけるRXRの発現と局在2016

    • Author(s)
      吉原大輔、釘田雅則、長尾静子
    • Organizer
      第59回日本腎臓学会学術総会
    • Place of Presentation
      神奈川県、横浜 パシフィコ横浜
    • Year and Date
      2016-06-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 多発性嚢胞腎症モデル動物の腎臓におけるレチノイドX受容体の解析2016

    • Author(s)
      釘田雅則、吉原大輔、加藤由布、小木曽昇、下村恭代、西田修、長尾静子
    • Organizer
      第63回日本実験動物学会総会
    • Place of Presentation
      神奈川県、川崎  ミューザ川崎シンフォニーホール
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report
  • [Presentation] Retinoid X receptor pathway, a novel signaling cascade responsible for cystogenesis in three rodent models of polycystic kidney disease.2015

    • Author(s)
      Yoshihara D, Kugita M, Aukema HM, Yamaguchi T, Nagao S.
    • Organizer
      American Society of Nephrology Kidney Week 2015
    • Place of Presentation
      San Diego, CA, U.S.A.
    • Year and Date
      2015-11-03
    • Related Report
      2015 Research-status Report
  • [Presentation] であるPCKラットにおけるGi作動薬の病態進行2015

    • Author(s)
      吉原大輔、釘田雅則、西井一宏、鈴木敦詞、湯澤由紀夫、東原英二、堀江重郎、山口太美雄、長尾静子
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report
  • [Presentation] 多発性嚢胞腎症のモデル動物であるPCKラットにおけるGi作動薬の病態進行抑制効果2015

    • Author(s)
      釘田雅則、吉原大輔、西井一宏、鈴木敦詞、湯澤由紀夫、山口太美雄、堀江重郎、東原英二、長尾静子
    • Organizer
      第62回日本実験動物学会総会
    • Place of Presentation
      京都
    • Year and Date
      2015-05-28
    • Related Report
      2015 Research-status Report
  • [Presentation] Expression and distribution of retinoid X receptor in rodent models of polycystic kidney disease.2015

    • Author(s)
      Yoshihara D, Kugita M, Sasaki M, Nagao S.
    • Organizer
      11th ASPR Congress & the 118th Annual Meeting of the Japan Pediatric Society
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2015-04-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Beneficial effect of combined treatment of two somatostatin analogs in an orthologous model of human autosomal recessive polycystic kidney disease.2015

    • Author(s)
      Yoshihara D, Kugita M, Sasaki M, Nishii K, Suzuki A, Higashihara E, Horie S, Yamaguchi T, Nagao S.
    • Organizer
      1th ASPR Congress & the 118th Annual Meeting of the Japan Pediatric Society
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2015-04-15
    • Related Report
      2015 Research-status Report
  • [Remarks]

    • URL

      http://www.fujita-hu.ac.jp/CAMHD/LAS/TOPICS.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 藤田保健衛生大学 疾患モデル科学

    • URL

      http://www.fujita-hu.ac.jp/CAMHD/LAS/index.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 藤田保健衛生大学 疾患モデル科学

    • URL

      http://www.fujita-hu.ac.jp/CAMHD/LAS/TOPICS.html

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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