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Comprehensive regulatory system of oxygen circulation in renal erythropoietin producing cells

Research Project

Project/Area Number 17K19680
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Internal medicine of the bio-information integration and related fields
Research InstitutionTohoku University

Principal Investigator

Suzuki Norio  東北大学, 医学系研究科, 准教授 (20447254)

Project Period (FY) 2017-06-30 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywords貧血 / 遺伝子改変マウス / エリスロポエチン / 腎臓病 / 高血圧 / 赤血球 / 循環 / 低酸素
Outline of Final Research Achievements

Blood pressure is tightly correlated with erythrocyte mass. However, the mechanisms responding to blood pressure decrease under anaemic conditions have not been investigated. In this study, we confirmed that blood pressure is lowered under anaemic conditions in human patients and mouse models. Whereas "JG cells" in kidneys are known as the major renin-producing cells, we have discovered that peritubular interstitial fibroblasts in kidneys induce renin production in response to anaemic hypotension. Interestingly, a part of the interstitial fibroblasts simultaneously produces renin and the erythropoietic cytokine EPO in anaemic mouse kidneys. These results propose that renal interstitial fibroblasts maintain systemic oxygen delivery through controlling production of renin and EPO.

Academic Significance and Societal Importance of the Research Achievements

レニンは血圧を制御する主要な因子であり、腎臓の傍糸球体細胞から分泌されることが多くの教科書に記載されている。本研究では、新たなレニン産生細胞として、尿細管間質線維芽細胞を同定した。また、数が限られている傍糸球体細胞によるレニン産生を補うために、血圧低下時に尿細管間質線維芽細胞がレニンを産生することを提唱した。さらに、赤血球造血因子EPOとレニンを同時に産生する尿細管間質線維芽細胞の重要な役割を解明した。非常に多くの女性が加齢とともに貧血を患うが、本研究の成果は加齢性の貧血による血圧低下の機序の一端を明らかにした。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (45 results)

All 2020 2019 2018 2017 2016 Other

All Int'l Joint Research (8 results) Journal Article (16 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 16 results,  Open Access: 9 results,  Acknowledgement Compliant: 2 results) Presentation (20 results) (of which Int'l Joint Research: 4 results,  Invited: 14 results) Book (1 results)

  • [Int'l Joint Research] 国立台湾大学(その他の国・地域)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Karolinska Institute(スウェーデン)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] National University of Singapore(シンガポール)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Vanderbilt University(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Karolinska Institute(スウェーデン)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] National University of Singapore(シンガポール)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Harvard University(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Karolinska Institute(Sweden)

    • Related Report
      2017 Research-status Report
  • [Journal Article] An immortalized cell line derived from renal erythropoietin-producing (REP) cells demonstrates their potential to transform into myofibroblasts2019

    • Author(s)
      Sato Koji、Hirano Ikuo、Sekine Hiroki、Miyauchi Kenichiro、Nakai Taku、Kato Koichiro、Ito Sadayoshi、Yamamoto Masayuki、Suzuki Norio
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 11254-11254

    • DOI

      10.1038/s41598-019-47766-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Neural Crest as the First Production Site of the Erythroid Growth Factor Erythropoietin2019

    • Author(s)
      Hirano Ikuo、Suzuki Norio
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 7 Pages: 105-105

    • DOI

      10.3389/fcell.2019.00105

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alteration of the DNA Methylation Signature of Renal Erythropoietin-Producing Cells Governs the Sensitivity to Drugs Targeting the Hypoxia-Response Pathway in Kidney Disease Progression2019

    • Author(s)
      Sato Koji、Kumagai Naonori、Suzuki Norio
    • Journal Title

      Frontiers in Genetics

      Volume: 10 Pages: 1134-1134

    • DOI

      10.3389/fgene.2019.01134

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HIF-dependent and reversible nucleosome disassembly in hypoxia-inducible gene promoters.2018

    • Author(s)
      Suzuki N, Vojnovic N, Lee KL, Yang H, Gradin K, Poellinger L.
    • Journal Title

      Exp Cell Res

      Volume: 366 Issue: 2 Pages: 181-191

    • DOI

      10.1016/j.yexcr.2018.03.020

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Palmitate deranges erythropoietin production via transcription factor ATF4 activation of unfolded protein response2018

    • Author(s)
      Anusornvongchai Thitinun、Nangaku Masaomi、Jao Tzu-Ming、Wu Chia-Hsien、Ishimoto Yu、Maekawa Hiroshi、Tanaka Tetsuhiro、Shimizu Akira、Yamamoto Masayuki、Suzuki Norio、Sassa Ryoji、Inagi Reiko
    • Journal Title

      Kidney International

      Volume: 94 Issue: 3 Pages: 536-550

    • DOI

      10.1016/j.kint.2018.03.011

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] O-GlcNAcylation Signal Mediates Proteasome Inhibitor Resistance in Cancer Cells by Stabilizing NRF12018

    • Author(s)
      Sekine Hiroki、Okazaki Keito、Kato Koichiro、Alam M. Morshedul、Shima Hiroki、Katsuoka Fumiki、Tsujita Tadayuki、Suzuki Norio、Kobayashi Akira、Igarashi Kazuhiko、Yamamoto Masayuki、Motohashi Hozumi
    • Journal Title

      Molecular and Cellular Biology

      Volume: 38 Issue: 17 Pages: 00252-18

    • DOI

      10.1128/mcb.00252-18

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Iron attenuates erythropoietin production by decreasing hypoxia-inducible transcription factor 2α concentrations in renal interstitial fibroblasts2018

    • Author(s)
      Suzuki Norio、Matsuo-Tezuka Yukari、Sasaki Yusuke、Sato Koji、Miyauchi Kenichiro、Kato Koichiro、Saito Sakae、Shimonaka Yasushi、Hirata Michinori、Yamamoto Masayuki
    • Journal Title

      Kidney International

      Volume: 94 Issue: 5 Pages: 900-911

    • DOI

      10.1016/j.kint.2018.06.028

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] エリスロポエチンによる赤血球造血制御のメカニズム2018

    • Author(s)
      鈴木教郎
    • Journal Title

      血液フロンティア

      Volume: 28 Pages: 1301-1308

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 腎障害によるエリスロポエチン産生低下の分子機構2018

    • Author(s)
      宮内健一郎, 鈴木教郎
    • Journal Title

      腎臓内科・泌尿器科

      Volume: 8 Pages: 103-107

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 腎エリスロポエチン産生細胞と腎線維化2018

    • Author(s)
      佐藤浩司, 鈴木教郎
    • Journal Title

      腎臓内科・泌尿器科

      Volume: 7 Pages: 357-362

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 酸素恒常性維持における赤血球造血系の役割とその破綻による病態への影響2018

    • Author(s)
      鈴木教郎
    • Journal Title

      臨床病理

      Volume: 66 Pages: 86-93

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 生体内酸素環境と赤血球造血制御系の相互作用2018

    • Author(s)
      鈴木教郎
    • Journal Title

      細胞

      Volume: 50 Pages: 18-21

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of hypoxia-inducible gene expression after HIF activation2017

    • Author(s)
      Suzuki Norio、Gradin Katarina、Poellinger Lorenz、Yamamoto Masayuki
    • Journal Title

      Exp Cell Res

      Volume: 356 Issue: 2 Pages: 182-186

    • DOI

      10.1016/j.yexcr.2017.03.013

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Renal Anemia Model Mouse Established by Transgenic Rescue with an Erythropoietin Gene Lacking Kidney-Specific Regulatory Elements2017

    • Author(s)
      Hirano I, Suzuki N, Yamazaki S, Sekine H, Minegishi N, Shimizu R, Yamamoto M.
    • Journal Title

      Mol Cell Biol

      Volume: 37 Issue: 4

    • DOI

      10.1128/mcb.00451-16

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Nrf2 inactivation enhances placental angiogenesis in a preeclampsia mouse model and improves maternal and fetal outcomes2017

    • Author(s)
      Nezu Masahiro、Souma Tomokazu、Yu Lei、Sekine Hiroki、Takahashi Nobuyuki、Wei Andrew Zu-Sern、Ito Sadayoshi、Fukamizu Akiyoshi、Zsengeller Zsuzsanna K.、Nakamura Tomohiro、Hozawa Atsushi、Karumanchi S. Ananth、Suzuki Norio、Yamamoto Masayuki
    • Journal Title

      Sci Signal

      Volume: 10 Issue: 479

    • DOI

      10.1126/scisignal.aam5711

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transcription factor Nrf2 hyperactivation in early-phase renal ischemia-reperfusion injury prevents tubular damage progression2016

    • Author(s)
      Nezu M, Souma T, Yu L, Suzuki T, Saigusa D, Ito S, Suzuki N, Yamamoto M.
    • Journal Title

      Kidney Int

      Volume: 91 Issue: 2 Pages: 387

    • DOI

      10.1016/j.kint.2016.08.023

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Induction of erythropoietin and renin production in kidneys under anemic conditions to maintain oxygen homeostasis2019

    • Author(s)
      宮内健一郎, 伊藤貞嘉, 山本雅之, 鈴木教郎
    • Organizer
      第62回 日本腎臓学会学術集会シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 腎臓病における『REP細胞』の関与2019

    • Author(s)
      鈴木教郎
    • Organizer
      第62回 日本腎臓学会学術集会ランチョンセミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 腎エリスロポエチン産生不全の分子機序2019

    • Author(s)
      鈴木教郎
    • Organizer
      第64回 日本透析医学会学術集会ワークショップ
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Hypoxia-inducible Epo gene regulation in renal erythropoietin producing (REP) cells and its association with iron metabolism, erythropoiesis, and disease2019

    • Author(s)
      Norio Suzuki
    • Organizer
      Seminar in National Taiwan University
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] エリスロポエチン産生制御と体内鉄動態の連動機構2019

    • Author(s)
      鈴木教郎
    • Organizer
      第28回腎とエリスロポエチン研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] A cell line derived from renal erythropoietin-producing cells provese their myofibroblast-transformation property+2019

    • Author(s)
      Sato, K, Hirano, I, Sekine, H, Miyauchi, K, Nakai, T, Kato, K, Ito, S, Yamamoto, M, Suzuki, N
    • Organizer
      International Society of Nephrology World Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腎臓エリスロポエチン産生細胞『REP細胞』の正常と病態の分子機構2018

    • Author(s)
      鈴木教郎
    • Organizer
      沖縄県腎フォーラム特別講演会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 低酸素・酸化ストレスと腎臓線維化2018

    • Author(s)
      鈴木教郎
    • Organizer
      第2回Fibrosis
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 腎エリスロポエチン産生細胞『REP細胞』2018

    • Author(s)
      鈴木教郎
    • Organizer
      第10回OCU-CKD研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Erythropoietic induction in response to systemic hypoxia through renal erythropoietin producing (REP) cells2018

    • Author(s)
      鈴木教郎
    • Organizer
      WCP2018 KYOTO Satellite Symposia
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 赤血球増殖因子エリスロポエチンの低酸素誘導的産生制御機構2018

    • Author(s)
      鈴木教郎
    • Organizer
      第91回日本生化学会大会シンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Maintenance of oxygen homeostasis by erythropoietic regulation and its disorder related to diseases2018

    • Author(s)
      Koji Sato, Norio Suzuki
    • Organizer
      Keystone Symposium on Adaptations to Hypoxia in Physiology and Disease
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腎エリスロポエチン産生細胞 「REP細胞」の細胞株樹立と腎臓線維化機構の解析2018

    • Author(s)
      佐藤浩司, 平野育生, 関根弘樹, 宮内健一郎, 加藤幸一郎, 伊藤貞嘉, 山本雅之, 鈴木教郎
    • Organizer
      日本生化学会東北支部 第84回例会・シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] 腎エリスロポエチン産生細胞 (REP細胞) 由来の細胞株は細胞自律性TGFβ発現により筋線維芽細胞の形質を有する2018

    • Author(s)
      佐藤浩司, 平野育生, 関根弘樹, 宮内健一郎, 加藤幸一郎, 伊藤貞嘉, 山本雅之, 鈴木教郎
    • Organizer
      第91回日本生化学会大会シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] 貧血による血圧低下と腎エリスロポエチン細胞におけるレニン産生誘導2018

    • Author(s)
      宮内健一郎, 伊藤貞嘉, 山本雅之, 鈴木教郎
    • Organizer
      第27回腎とエリスロポエチン研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 腎臓における低酸素・酸化ストレス応答機構2017

    • Author(s)
      鈴木教郎
    • Organizer
      広島大学 分子細胞情報学セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 低酸素と酸化ストレスに対する生体防御機構の腎臓での役割2017

    • Author(s)
      鈴木教郎
    • Organizer
      日本腎臓学会 シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 個体の酸素恒常性維持機構とその破綻による疾患への影響2017

    • Author(s)
      鈴木教郎
    • Organizer
      国立国際医療研究センター研究所セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 酸素恒常性維持における赤血球造血系の役割とその破綻による病態への影響2017

    • Author(s)
      鈴木教郎
    • Organizer
      第57回日本臨床化学会年次学術集会 教育講演
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 貧血は低血圧を招来し腎レニン発現を誘導する2017

    • Author(s)
      宮内健一郎 加藤幸一郎 袮津昌広 齋藤さかえ 佐藤浩司 山本雅之 鈴木教郎
    • Organizer
      ConBio 2017
    • Related Report
      2017 Research-status Report
  • [Book] アンチ・ドーピング 徹底解説! スポーツ医薬-服薬指導とその根拠(鈴木秀典、赤間高雄、亀井美和子 編)2020

    • Author(s)
      中井琢, 鈴木教郎, 山本雅之
    • Total Pages
      260
    • Publisher
      中山書店
    • ISBN
      9784521747934
    • Related Report
      2019 Annual Research Report

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Published: 2017-07-21   Modified: 2022-02-21  

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