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2020 Fiscal Year Research-status Report

A pathophysiological significance of receptor-binding factor in aging-associated cerebral cardiovascular disease

Research Project

Project/Area Number 20K07786
Research InstitutionYokohama City University

Principal Investigator

涌井 広道  横浜市立大学, 医学部, 講師 (10587330)

Co-Investigator(Kenkyū-buntansha) 山下 暁朗  横浜市立大学, 医学研究科, 客員教授 (20405020)
田村 功一  横浜市立大学, 医学研究科, 教授 (40285143)
Project Period (FY) 2020-04-01 – 2023-03-31
Keywordsレニン-アンジオテンシン系 / 慢性腎臓病 / アンチエイジング
Outline of Annual Research Achievements

本研究では,受容体結合蛋白ATRAP (AT1 receptor-associated protein)について、アンジオテンシン受容体結合性機能選択的制御作用、及びアンジオテンシン受容体結合に依存しない可能性のある腎臓線維化抑制作用に着目して、老化モデル動物,ATRAP遺伝子改変動物などを用いて、ATRAPの発現・活性調節機構異常と老化関連脳心血管腎臓病との関連について多面的に検討し、ATRAP の老化関連脳心血管腎臓病における病態生理学的意義の解明、および ATRAP に着目した新規分子標的治療法の開発に向けた検討を行う。
野生型C57BL/6マウスに対して、薬剤X投与による腎障害モデルを複数のプロトコールで作製した。その結果、腎萎縮、尿細管間質線維化、腎機能低下、細胞老化の促進、ミトコンドリア機能異常、抗老化遺伝子発現の低下といった老化腎を模倣する最適のプロトコルを確立した。腎臓近位尿細管特異的ATRAP高発現マウスの作製に成功し、薬剤性腎老化誘導モデルをもちいて、近位尿細管ATRAPの抗老化、抗線維化メカニズムの解析を行っている。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

薬剤誘導性腎老化モデルの確立に成功した。本モデルをもちいて、尿細管ATRAPの腎性老化における機能的意義を効率よく検討可能である。

Strategy for Future Research Activity

尿細管特異的ATRAP高発現マウスをもちいて、ATRAPの腎性老化、腎線維化に対する改善作用をその機序も含めて解析する。さらに、ATRAP新規結合因子についての探索もすすめる。

Causes of Carryover

試薬代の値引きにより179円の繰り越しが生じた

  • Research Products

    (15 results)

All 2021 2020

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 7 results) Presentation (1 results)

  • [Journal Article] A case of minimal change nephrotic syndrome with pregnancy2021

    • Author(s)
      Horigome Mari、Kobayashi Ryu、Hanaoka Masaaki、Kinguchi Sho、Kanaoka Tomohiko、Toya Yoshiyuki、Wakui Hiromichi、Tamura Kouichi
    • Journal Title

      CEN Case Reports

      Volume: 印刷中 Pages: 印刷中

    • DOI

      10.1007/s13730-020-00568-5

    • Peer Reviewed
  • [Journal Article] Cardiovascular and renal outcomes with SGLT-2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and network meta-analysis2021

    • Author(s)
      Yamada Takayuki、Wakabayashi Mako、Bhalla Abhinav、Chopra Nitin、Miyashita Hirotaka、Mikami Takahisa、Ueyama Hiroki、Fujisaki Tomohiro、Saigusa Yusuke、Yamaji Takahiro、Azushima Kengo、Urate Shingo、Suzuki Toru、Abe Eriko、Wakui Hiromichi、Tamura Kouichi
    • Journal Title

      Cardiovascular Diabetology

      Volume: 20 Pages: 14

    • DOI

      10.1186/s12933-020-01197-z

    • Peer Reviewed / Open Access
  • [Journal Article] Relationship between basal sodium intake and the effects of dapagliflozin in albuminuric diabetic kidney disease2021

    • Author(s)
      Kinguchi Sho、Wakui Hiromichi、Ito Yuzuru、Kondo Yoshinobu、Azushima Kengo、Osada Uru、Yamakawa Tadashi、Iwamoto Tamio、Yutoh Jun、Misumi Toshihiro、Yasuda Gen、Yoshii Taishi、Haruhara Kotaro、Kobayashi Yusuke、Yamanaka Takeharu、Terauchi Yasuo、Tamura Kouichi
    • Journal Title

      Scientific Reports

      Volume: 11 Pages: 951

    • DOI

      10.1038/s41598-020-79687-z

    • Peer Reviewed / Open Access
  • [Journal Article] Tissue xanthine oxidoreductase activity in a mouse model of aristolochic acid nephropathy2021

    • Author(s)
      Ishii Takeo、Kumagae Tomohiro、Wakui Hiromichi、Urate Shingo、Tanaka Shohei、Abe Eriko、Suzuki Toru、Yamaji Takahiro、Kinguchi Sho、Kobayashi Ryu、Haruhara Kotaro、Nakamura Takashi、Kobayashi Shuzo、Tamura Kouichi
    • Journal Title

      FEBS Open Bio

      Volume: 11 Pages: 507~518

    • DOI

      10.1002/2211-5463.13083

    • Peer Reviewed / Open Access
  • [Journal Article] Preliminary Report: The Relevance of Tumor Necrosis Factor-α in Acquired Primary Lymphedema?A Histopathological Investigation2020

    • Author(s)
      Asano Saori、Mikami Taro、Matsubara Shinobu、Maegawa Jiro、Wakui Hiromichi、Tamura Kouichi、Yoshimi Ryusuke
    • Journal Title

      Lymphatic Research and Biology

      Volume: 18 Pages: 232~238

    • DOI

      10.1089/lrb.2019.0046

    • Peer Reviewed / Open Access
  • [Journal Article] The circadian clock is disrupted in mice with adenine-induced tubulointerstitial nephropathy2020

    • Author(s)
      Motohashi Hiroaki、Tahara Yu、Whittaker Daniel S.、Wang Huei-Bin、Yamaji Takahiro、Wakui Hiromichi、Haraguchi Atsushi、Yamazaki Mayu、Miyakawa Hiroki、Hama Koki、Sasaki Hiroyuki、Sakai Tomoko、Hirooka Rina、Takahashi Kengo、Takizawa Miku、Makino Saneyuki、Aoyama Shinya、Colwell Christopher S.、Shibata Shigenobu
    • Journal Title

      Kidney International

      Volume: 97 Pages: 728~740

    • DOI

      10.1016/j.kint.2019.09.032

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effects of Rikkunshito treatment on renal fibrosis/inflammation and body weight reduction in a unilateral ureteral obstruction model in mice2020

    • Author(s)
      Wakui Hiromichi、Yamaji Takahiro、Azushima Kengo、Uneda Kazushi、Haruhara Kotaro、Nakamura Akiko、Ohki Kohji、Kinguchi Sho、et al
    • Journal Title

      Scientific Reports

      Volume: 10 Pages: 1782

    • DOI

      10.1038/s41598-020-58214-0

    • Peer Reviewed / Open Access
  • [Journal Article] Mass clinical survey as a possible population strategy for the better control of hypertension in Japan2020

    • Author(s)
      Tamura Kouichi、Yamaji Takahiro、Azushima Kengo、Wakui Hiromichi
    • Journal Title

      Hypertension Research

      Volume: 43 Pages: 463~465

    • DOI

      10.1038/s41440-019-0381-9

    • Peer Reviewed
  • [Journal Article] The pathophysiological role of angiotensin receptor-binding protein in hypertension and kidney diseases: Oshima Award Address 20192020

    • Author(s)
      Wakui Hiromichi
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 24 Pages: 289~294

    • DOI

      10.1007/s10157-020-01861-4

    • Peer Reviewed
  • [Journal Article] Low‐density‐lipoprotein apheresis‐mediated endothelial activation therapy to severe‐peripheral artery disease study: Rationale and study design2020

    • Author(s)
      Ueda Eiko、Toya Yoshiyuki、Wakui Hiromichi、Kawai Yuki、Azushima Kengo、Fujita Takayuki、Saigusa Yusuke、Yamanaka Takeharu、Yabuki Yuichiro、Mikami Taro、Goda Motohiko、Sugano Teruyasu、Tamura Kouichi
    • Journal Title

      Therapeutic Apheresis and Dialysis

      Volume: 24 Pages: 524~529

    • DOI

      10.1111/1744-9987.13546

    • Peer Reviewed
  • [Journal Article] Effect of renin-angiotensin system blockers on contrast-induced acute kidney injury in patients with normal or mild-to-moderate reduced kidney function undergoing coronary angiography: A?systematic review and meta-analysis2020

    • Author(s)
      Yamada Takayuki、Fujisaki Tomohiro、Chopra Nitin、Yamaji Takahiro、Azushima Kengo、Kobayashi Ryu、Kinguchi Sho、Urate Shingo、Suzuki Toru、Abe Eriko、Wakui Hiromichi、Tamura Kouichi、Steinberg Daniel
    • Journal Title

      Clinical Nephrology

      Volume: 94 Pages: 227~236

    • DOI

      10.5414/CN110171

    • Peer Reviewed
  • [Journal Article] Effects of Erythropoietin-Stimulating Agents on Blood Pressure in Patients with Non-Dialysis CKD and Renal Anemia2020

    • Author(s)
      Ohki Kohji、Wakui Hiromichi、Uneda Kazushi、Azushima Kengo、Haruhara Kotaro、Kinguchi Sho、Urate Shingo、Yamada Takayuki、Yamaji Takahiro、Kobayashi Ryu、Kanaoka Tomohiko、Minegishi Shintaro、Ishigami Tomoaki、Fujikawa Tetsuya、Toya Yoshiyuki、Tamura Kouichi
    • Journal Title

      Kidney Diseases

      Volume: 6 Pages: 299~308

    • DOI

      10.1159/000507396

    • Peer Reviewed / Open Access
  • [Journal Article] Systematic Review of the Association Between Worsening Renal Function and Mortality in Patients With Acute Decompensated Heart Failure2020

    • Author(s)
      Yamada Takayuki、Ueyama Hiroki、Chopra Nitin、Yamaji Takahiro、Azushima Kengo、Kobayashi Ryu、Kinguchi Sho、Urate Shingo、Suzuki Toru、Abe Eriko、Saigusa Yusuke、Wakui Hiromichi、Partridge Paulina、Burger Alfred、Bravo Claudio A.、Rodriguez Maria A.、Ivey-Miranda Juan、Tamura Kouichi、Testani Jeffery、Coca Steven
    • Journal Title

      Kidney International Reports

      Volume: 5 Pages: 1486~1494

    • DOI

      10.1016/j.ekir.2020.06.031

    • Peer Reviewed / Open Access
  • [Journal Article] May need more comprehensive approach to residual risks in well controlled hypertensive patients2020

    • Author(s)
      Suzuki Toru、Kamimura Daisuke、Wakui Hiromichi、Tamura Kouichi
    • Journal Title

      Hypertension Research

      Volume: 44 Pages: 253~255

    • DOI

      10.1038/s41440-020-00567-0

    • Peer Reviewed
  • [Presentation] 受容体結合タンパク(ATRAP)による血圧と臓器障害制御 Up date2020

    • Author(s)
      涌井広道
    • Organizer
      第63回日本腎臓学会学術総会

URL: 

Published: 2021-12-27  

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