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Physiological and molecular mechanisms underlying renal congestion in congestive heart failure

Research Project

Project/Area Number 16H05312
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionTohoku Medical and Pharmaceutical University

Principal Investigator

MORI Takefumi  東北医科薬科大学, 医学部, 教授 (40375001)

Co-Investigator(Kenkyū-buntansha) 佐藤 恵美子  東北大学, 薬学研究科, 助教 (20466543)
伊藤 貞嘉  東北大学, 医学系研究科, 教授 (40271613)
大崎 雄介  東北大学, 大学病院, その他 (40509212)
矢花 郁子  東北医科薬科大学, 医学部, 助教 (60778596)
Research Collaborator SHIMADA Satoshi  
TAKAHASHI Chika  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywords腎うっ血 / 腎循環 / 腎間質圧 / 腎間質線維化 / 心不全 / 腎臓生理学 / V-ATPase / TGF-β / 線維化
Outline of Final Research Achievements

We created a rat renal congestion model and investigated the effect of renal congestion on hemodynamics and molecular mechanisms. Tubulointerstitial injury and medullary thick ascending limb hypoxia were observed only in the congestive kidneys. Using this rat congestion model and cell culture system, we revealed that vacuolar ATPase system in acidic organelles and pericyte injury were involved in the development of renal interstitial fibrosis due to renal congestion.

Academic Significance and Societal Importance of the Research Achievements

本研究により、腎うっ血における腎間質線維化機序が明らかとなった。これにより体液貯留を呈する疾患における腎保護をしながら調節する治療法や治療の代用指標を解明することが可能となった。これまで、腎循環は動脈血流を中心として研究され、降圧剤など動脈圧を調節する薬剤が開発されており、腎静脈循環を調節する薬剤は開発されていない。本研究成果により、腎うっ血に伴う腎臓障害に酸性オルガネラにおけるタンパク質輸送の障害や直血管の障害が関与していることが示唆された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (47 results)

All 2019 2018 2017 2016 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (39 results) (of which Int'l Joint Research: 11 results,  Invited: 4 results) Remarks (1 results)

  • [Journal Article] Low-energy extracorporeal shock wave ameliorates ischemic acute kidney injury in rats2019

    • Author(s)
      Yoshida Mai、Nakamichi Takashi、Mori Takefumi、Ito Kenta、Shimokawa Hiroaki、Ito Sadayoshi
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 23 Issue: 5 Pages: 597-605

    • DOI

      10.1007/s10157-019-01689-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment of renal congestion by tolvaptan2019

    • Author(s)
      Mori Takefumi、Hirose Takuo、Kinugasa Satoshi
    • Journal Title

      Hypertension Research

      Volume: 42 Issue: 5 Pages: 745-748

    • DOI

      10.1038/s41440-019-0215-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hydrochlorothiazide ameliorates polyuria caused by tolvaptan treatment of polycystic kidney disease in PCK rats2018

    • Author(s)
      Wang Anyi、Hirose Takuo、Ohsaki Yusuke、Takahashi Chika、Sato Emiko、Oba-Yabana Ikuko、Kinugasa Satoshi、Muroya Yoshikazu、Ito Sadayoshi、Mori Takefumi
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 23 Issue: 4 Pages: 455-464

    • DOI

      10.1007/s10157-018-1669-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathophysiological and molecular mechanisms involved in renal congestion in a novel rat model2018

    • Author(s)
      Shimada Satoshi、Hirose Takuo、Takahashi Chika、Sato Emiko、Kinugasa Satoshi、Ohsaki Yusuke、Kisu Kiyomi、Sato Hiroshi、Ito Sadayoshi、Mori Takefumi
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 16808-16808

    • DOI

      10.1038/s41598-018-35162-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Urinary angiotensinogen excretion level is associated with elevated blood pressure in the normotensive general population.2018

    • Author(s)
      Sato E, Wang AY, Satoh M, Nishikiori Y, Oba-Yabana I, Yoshida M, Sato H, Ito S, Hida W, Mori T
    • Journal Title

      Am J Hypertens

      Volume: - Issue: 6 Pages: 742-749

    • DOI

      10.1093/ajh/hpy020

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acidic organelles mediate TGF-β1-induced cellular fibrosis via (pro)renin receptor and vacuolar ATPase trafficking in human peritoneal mesothelial cells.2018

    • Author(s)
      1: Oba-Yabana I, Mori T, Takahashi C, Hirose T, Ohsaki Y, Kinugasa S, Muroya Y, Sato E, Nguyen G, Piedagnel R, Ronco PM, Totsune K, Ito S
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 2648-2648

    • DOI

      10.1038/s41598-018-20940-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diuretic Usage for Protection against End-Organ Damage in Liver Cirrhosis and Heart Failure.2016

    • Author(s)
      Mori T, Osaki Y, Oba-Yabana I, Ito S.
    • Journal Title

      Hepatol Res.

      Volume: 印刷中 Issue: 1 Pages: 11-22

    • DOI

      10.1111/hepr.12700

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ラット腎うっ血モデルにおける(プロ)レニン受容体の発現2019

    • Author(s)
      松木琢磨, 廣瀬卓男, 島田佐登志, 髙橋知香, 矢花郁子, 中村はな, 衣笠哲史, 室谷嘉一, 谷淳一, 伊藤貞嘉, 森建文
    • Organizer
      第11回(プロ)レニン受容体フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] ラット腎臓光学顕微鏡用組織標本の低真空走査電子顕微鏡での観察2019

    • Author(s)
      廣瀬卓男, 衣笠哲史, 髙橋知香, 矢花郁子, 中村はな, 室谷嘉一, 谷淳一, 森建文
    • Organizer
      第64回日本透析医学会学術集会・総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] エクソン4欠失(プロ)レニン受容体のV-ATPase機能に与える影響2019

    • Author(s)
      廣瀬卓男, 松木琢磨, 髙橋知香, 矢花郁子, 中村はな, 衣笠哲史, 室谷嘉一, 谷淳一, 森建文
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 腎うっ血における(プロ)レニン受容体の発現2019

    • Author(s)
      廣瀬卓男, 島田佐登志, 松木琢磨, 髙橋知香, 矢花郁子, 中村はな, 衣笠哲史, 室谷嘉一, 谷淳一, 森建文
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Expressoin of (pro)renin receptor in rat renal congestion model2019

    • Author(s)
      Hirose T, Shimada S, Matsuki T, Takahashi C, Nakamura H, Kinugasa S, Muroya Y, Tani J, Mori T
    • Organizer
      World Congress of Nephrology 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Low-vacuum scanning electron microscopy analysis for formalin-fixed paraffin-embedded rat kidney sections2019

    • Author(s)
      Moriyama S, Takeuchi W, Kaburaki T, Shimada K, Hirose T, Kinugasa S, Matsuki T, Oba-Yabana I, Muroya Y, Mori T
    • Organizer
      World Congress of Nephrology 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Imatinib attenuates perycite-myofibroblast transition in renal congestion in rats2019

    • Author(s)
      Matsuki T, Hirose T, Shimada S, Takahashi C, Kinugasa S, Muroya Y, Nakamura H, Tani J, Mori T
    • Organizer
      World Congress of Nephrology 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] N-terminal pro-B-type natriuretic peptides is a predictor of chronic kidney disease incidence in an Asian general population: The Ohasama study2019

    • Author(s)
      Nakayama S, Satoh M, Metoki H, Murakami T, Kikuya M, Mori T, Hozawa A, Node K, Imai Y, Ohkubo T
    • Organizer
      World Congress of Nephrology 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Exon 4-encoded domain of (pro)renin receptor impairs several V-ATPase-mediated functions2019

    • Author(s)
      Hirose T, Cabrera-Socorro A, Matsuki T, Takahashi C, Oba-Yabana I, Kinugasa S, Muroya Y, Tani J, Nguyen G, Groszer M, Ito S, Mori T
    • Organizer
      International Symposium for Aldosterone and Related Substances in Hypertension 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pericyte-myofibroblast transition induced tubulo-interstitial injury in a novel rat venous congestion rat model2018

    • Author(s)
      Hirose T, Shimada S, Takahashi C, Sato E, Kinugasa S, Ito S, Mori T
    • Organizer
      ASN Kidney Week 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Renal ischemia-reperfusion injury in aging and diabetes2018

    • Author(s)
      Muroya Y, He X, Fan F, Mori T, Ito O, Roman RJ
    • Organizer
      Counsil on Hypertension
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pericyte detachment is involved in renal congestion in a novel rat model2018

    • Author(s)
      Shimada S, Hirose T, Takahashi C, Sato E, Kinugasa S, Ito S, Mori T
    • Organizer
      Counsil on Hypertension
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 臓器保護の観点から降圧利尿薬の意義を改めて考える2018

    • Author(s)
      森建文
    • Organizer
      第7回臨床高血圧フォーラム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 腎循環と内分泌2018

    • Author(s)
      森建文
    • Organizer
      第45回日本日本神経内分泌学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ラット腎うっ血モデルの作出とその腎障害機序の検討2018

    • Author(s)
      廣瀬卓男, 島田佐登志, 髙橋知香, 佐藤恵美子, 衣笠哲史, 金須清美, 佐藤博, 伊藤貞嘉, 森建文
    • Organizer
      第41回日本高血圧学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Dahl食塩感受性ラットの腎ネフロンセグメントにおける高食塩食摂取による(プロ)レニン受容体発現調節2018

    • Author(s)
      山越聖子, 伊藤修, 戎栄, 大崎雄介, 中村貴裕, 高橋和広, 室谷嘉一, 森建文, 伊藤貞嘉, 戸恒和人, 上月正博
    • Organizer
      第41回日本高血圧学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 腹膜中皮細胞における(プロ)レニン受容体の役割の検討2018

    • Author(s)
      廣瀬卓男, 矢花郁子, 髙橋知香, 衣笠哲史, 室谷嘉一, 伊藤貞嘉, 森建文
    • Organizer
      第63回日本透析医学会学術集会・総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Dahl食塩感受性ラットの近位尿細管における高食塩食摂取による(プロ)レニン受容体発現調節2018

    • Author(s)
      山越聖子, 伊藤修, 戎栄, 大崎雄介, 中村貴裕, 高橋和広, 室谷嘉一, 森建文, 伊藤貞嘉, 戸恒和人, 上月正博
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] うっ血により惹起される腎障害機序におけるカルボニルストレスの役割2018

    • Author(s)
      大崎雄介, 高橋知香, 伊藤貞嘉, 森建文
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 低真空走査電子顕微鏡によるラット腎臓光学顕微鏡用組織標本の検討2018

    • Author(s)
      廣瀬卓男, 衣笠哲史, 島田佐登志, 高橋知香, 矢花郁子, 大崎雄介, 室谷嘉一, 伊藤貞嘉, 森建文
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PCKラットにおけるトルバプタンにより誘導される水利尿作用へのサイアザイド系利尿薬の効果2018

    • Author(s)
      Wang Anyi, 大崎雄介, 廣瀬卓男, 高橋知香, 矢花郁子, 衣笠哲史, 室谷嘉一, 伊藤貞嘉, 森建文
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ポドサイト障害に対するV-ATPaseの評価2018

    • Author(s)
      松木琢磨, 森建文, 高橋知香, 矢花郁子, 大崎雄介, 廣瀬卓男, 熊谷直憲, 伊藤貞嘉
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 腎うっ血による腎障害機序の解明2018

    • Author(s)
      島田佐登志, 大崎雄介, 高橋知香, 廣瀬卓男, 佐藤恵美子, 伊藤貞嘉, 森建文
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 食塩感受性高血圧ラットにおける高食塩食による腎(プロ)レニン受容体発現2018

    • Author(s)
      山越聖子, 伊藤修, 戎栄, 大崎雄介, 中村貴裕, 高橋和広, 森建文, 室谷嘉一, 伊藤貞嘉, 戸恒和人, 上月正博.
    • Organizer
      第7回臨床高血圧フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Pathophysiological analysis of renal congestion using a novel rat model2018

    • Author(s)
      Satoshi Shimada, Yusuke Ohsaki, Chika Takahashi, Takuo Hirose, Emiko Sato, Sadayoshi Ito and Takefumi Mori
    • Organizer
      ISN Frontiers Meetings Kidney Disease and Cardiovascular Disease
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腎線維化における集合管酸性オルガネラの役割2017

    • Author(s)
      森 建文、高橋知香、矢花郁子、大崎雄介、衣笠哲史、伊藤貞嘉
    • Organizer
      第60回日本腎臓学会学術総会
    • Place of Presentation
      仙台国際会議場 (宮城県・仙台市)
    • Year and Date
      2017-05-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] 培養ポドサイト線維化機序に対するV-ATPaseの評価2017

    • Author(s)
      松木琢磨、森 建文、髙橋知香、矢花郁子、大崎雄介、熊谷直憲、伊藤貞嘉
    • Organizer
      第60回日本腎臓学会学術総会
    • Place of Presentation
      仙台国際会議場(宮城県・仙台市)
    • Year and Date
      2017-05-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] The effect of carbonyl stress on renal injury induced by renal congestion.2017

    • Author(s)
      Yusuke Ohsaki, Chika Takahashi, Takefumi Mori and Sadayoshi Ito
    • Organizer
      American Society of Hypertension Joint Scientific Sessions
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pathophysiological analysis of renal congestion using a novel rat models2017

    • Author(s)
      Shimada, Takefumi Mori, Yusuke Ohsaki , Chika Takahashi , Sadayoshi Ito
    • Organizer
      American Society of Nephrology Kidney Week
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腎髄質循環2017

    • Author(s)
      森 建文
    • Organizer
      第6回臨床高血圧フォーラム
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Invited
  • [Presentation] うっ血性心不全により誘導される腎障害に対する腎生理学的検討2017

    • Author(s)
      大崎雄介、森 建文、美間健二、王安邑、高橋知香、伊藤貞嘉
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 培養ポドサイト線維化機序に対するV-ATPaseの評価2017

    • Author(s)
      松木琢磨、森 建文、高橋知香、矢花郁子、大崎雄介、熊谷直憲、伊藤貞嘉
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] っ血による腎障害に対するカルボニルストレスの影響2017

    • Author(s)
      大崎雄介、高橋知香、森 建文、伊藤貞嘉
    • Organizer
      第40回日本高血圧学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Dahl 食塩感受性ラットの腎における高食塩食摂取、nitric oxide synthase 抑制による( プロ)レニン受容体発現2017

    • Author(s)
      山越 聖子、伊藤 修、戎 栄、大崎 雄介、中村 貴裕、室谷 嘉一、森 建文、伊藤 貞嘉、高橋 和広、戸恒 和人、上月 正博
    • Organizer
      第40回日本高血圧学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 腎うっ血による腎障害機序の解明2017

    • Author(s)
      島田佐登志、大崎雄介、高橋知香、伊藤貞嘉、森 建文
    • Organizer
      第8回腎不全研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 酸性オルガネラによる蛋白輸送は腹膜透析におけるグルコース分解産物(GDPs)誘導性腹膜線維化に関与する2017

    • Author(s)
      矢花郁子、大崎雄介、高橋知香、伊藤貞嘉、森 建文
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 食塩誘発性高血圧に体液過剰は必須か? ~肯定~2016

    • Author(s)
      森 建文
    • Organizer
      第39回日本高血圧学会総会
    • Place of Presentation
      仙台国際会議場(宮城県・仙台市)
    • Year and Date
      2016-09-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Dahl食塩感受性ラットの腎における高食塩飼料給餌による(プロ)レニン受容体発現調節異常2016

    • Author(s)
      山越聖子、伊藤修、戒 栄、大崎雄介、室谷嘉一、森 建文、伊藤貞嘉、高橋和広、戸恒和人、上月正博
    • Organizer
      第39回日本高血圧学会総会
    • Place of Presentation
      仙台国際会議場(宮城県・仙台市)
    • Year and Date
      2016-09-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] うっ血による腎障害機序の検討2016

    • Author(s)
      大崎 雄介、森建文、美間健二、王安邑、高橋知香、伊藤貞嘉
    • 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
    • Related Report
      2016 Annual Research Report
  • [Remarks] 東北医科薬科大学 内科学第三(腎臓内分泌内科)教室

    • URL

      https://tohokupd.jimdo.com

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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