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

• Project/Area Number: 15K08435
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Fujita 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: ¥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.

Research Products

• [Journal Article] Mitochondrial Abnormality Facilitates Cyst Formation in Autosomal Dominant Polycystic Kidney Disease (2017)
  • 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
  • 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
  • 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
  • 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 disease (2017)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
• [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
  • 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
  • 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
  • Int'l Joint Research
• [Presentation] Differential expressions of miR-378a-3p/ADAMTS1 in cpk mice, a model of ARPKD (2016)
  • 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
  • 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
• [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
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Remarks]
  • URL: http://www.fujita-hu.ac.jp/CAMHD/LAS/TOPICS.html
• [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
• [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