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Role of complement 3 in the pathogenesis of hypertension

Research Project

Project/Area Number 24591242
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionNihon University

Principal Investigator

FUKUDA Noboru  日本大学, 総合科学研究科, 教授 (40267050)

Co-Investigator(Kenkyū-buntansha) UENO Takahiro  日本大学, 医学部, 准教授 (40386008)
Co-Investigator(Renkei-kenkyūsha) NISHIYAMA Akira  香川大学, 医学部, 教授 (10325334)
MASHIMO Tomoji  京都大学, 医歯学系, 准教授 (80397554)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords高血圧 / 補体 / ジンクフィンガーヌクレアーゼ / 高血圧自然発症ラット / 上皮間葉化現象
Outline of Final Research Achievements

We investigated role of C3 in phenotype of mesenchymal cells and renal RA in SHR in vitro and in vivo. We investigated expression of renal C3, renin, TGF-β1 and LXRα and generation of Ang II in kidney of UUO model that shows EMT in C3 KO mice. We knock outed C3 gene from SHR/Izm by the zinc-finger nucleaze method and investigated blood pressure and phenotype in SHR. In wild type mice, C3 and renin were strongly stained in the degenerated nephrotubulus at same localization with increases in expression of C3 renin with increases in blood pressure in UUO model. In C3 KO mice, the EMT phenomen was suppressed with no expression of renin in UUO model. Blood pressure and body weight were significantly lower in C3 KO SHR. C3 is involved in the cardiovascular and renal remodelings in hypertension. C3 induces EMT of nephrotubulus and activation of renal RA system. C3 is a primary factor to activate the renal RA systems to induce hypertension in SHR.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (20 results)

All 2014 2013 2012

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (17 results) (of which Invited: 1 results)

  • [Journal Article] Role of complement 3a in the growth of mesangial cells from stroke-prone spontaneously hypertensive rats.2014

    • Author(s)
      Ikeda K, Fukuda N, Ueno T, Endo M, Kobayashi N, Soma M, Matsumoto K.
    • Journal Title

      Clinical and Experimental Hypertension

      Volume: 36(1) Issue: 1 Pages: 58-63

    • DOI

      10.3109/10641963.2013.789042

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Complement 3 activates the renal renin-angiotensin system by induction of epithelial-to-mesenchymal transition of the nephrotubulus in mice.2013

    • Author(s)
      Zhou X, Fukuda N, Matsuda H, Endo M, Wang X, Saito K, Ueno T, Matsumoto T, Matsumoto K, Soma M, Kobayashi N, Nishiyama A.
    • Journal Title

      American Journal of Physiology Renal Physiology

      Volume: 305(7)

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of complement 3a in the growth of mesangial cells from stroke-prone spontaneously hypertensive rats2013

    • Author(s)
      Ikeda K, Fukuda N, Ueno T, Endo M, Kobayashi N, Soma M, Matsumoto K
    • Journal Title

      Clinical and Experimental Hypertension

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] HR/Izm全ゲノムシーケンスでの補体C3構造とジンクフィンガーヌクレアーゼ(ZFN)法によるC3ノックアウトSHR/Izmの病態解析2014

    • Author(s)
      根岸英理子、福田 昇、片川まゆみ、上野高浩、相馬正義、真下知士
    • Organizer
      第50回 高血圧関連疾患モデル学会
    • Place of Presentation
      和歌山
    • Year and Date
      2014-12-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 補体C3は高血圧自然発症ラット(SHR)の間葉系組織を脱分化し組織RA系を介して高血圧を引き起こす2014

    • Author(s)
      根岸英理子、福田 昇、片川まゆみ、上野高浩、小松一俊、相馬正義、真下知士
    • Organizer
      第18回 日本心血管内分泌代謝学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Complement 3 is involved in hypertension by activation of renal RA systems in SHR2014

    • Author(s)
      Eriko Negishi, Noboru Fukuda, Takahiro Ueno, Masayoshi Soma
    • Organizer
      The 16th International SHR Symposium
    • Place of Presentation
      イタリア・ローマ
    • Year and Date
      2014-06-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Mesenchymal tissue dedifferentiation activating the local RAS in SHR2014

    • Author(s)
      Noboru Fukuda
    • Organizer
      The 16th International SHR Symposium
    • Place of Presentation
      イタリア・ローマ
    • Year and Date
      2014-06-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 腎尿細管上皮間葉化による腎臓内レニン・アンジオテンシン系の亢進2014

    • Author(s)
      福田 昇
    • Organizer
      第43回 日本心脈管作動物質学会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 腎尿細管上皮間葉化による腎臓内レニン・アンジオテンシン系の亢進.2013

    • Author(s)
      Zhou Xueli、福田 昇、上野高浩、相馬正義、西山 成
    • Organizer
      第86回 日本内分泌学会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 補体C3は上皮間葉化(EMT)により腎尿細管でのレニン-アンジオテンシン(RA)系を活性化する2013

    • Author(s)
      福田 昇、上野高浩、遠藤守人、松本紘一、相馬正義、西山 成
    • Organizer
      第56回 日本腎臓学会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Related Report
      2013 Research-status Report
  • [Presentation] 補体C3は腎髄質上皮間葉化現象(EMT)により腎内レニン・アンジオテンシン(RA)系を活性化し高血圧およぎ腎硬化症を引き起こす2013

    • Author(s)
      Zhou Xueli、福田 昇、上野高浩、遠藤守人、相馬正義、西山 成
    • Organizer
      第49回 高血圧関連疾患モデル学会
    • Place of Presentation
      日本大学会館(東京都千代田区)
    • Related Report
      2013 Research-status Report
  • [Presentation] 補体C3は腎尿細管上皮間葉化(EMT)により腎内レニン・アンジオテンシン(RA)系を活性化する2013

    • Author(s)
      福田 昇、上野高浩、松田裕之、西山 成、松本紘一、相馬正義
    • Organizer
      第42回 日本心脈管作動物質学会
    • Place of Presentation
      奈良
    • Related Report
      2012 Research-status Report
  • [Presentation] 補体C3a-C3a受容体系は腎間葉系細胞脱分化および上皮間葉化現象(EMT)に関与する2012

    • Author(s)
      福田 昇、Zhou Xueli、池田和也、上野高浩、松本太郎、相馬正義
    • Organizer
      第11回 再生医療学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 腎髄質尿細管上皮間葉化による補体C3を介した腎内レニン・アンジオテンシン系の活性化2012

    • Author(s)
      Zhou Xueli、福田 昇、上野高浩、遠藤守人、松田裕之、松本紘一、相馬正義
    • Organizer
      第35回 高血圧学会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] Role of C3a-C3a receptor system in cardiovascular and renal remodelings in SHR2012

    • Author(s)
      Kazuya Ikeda, Noboru Fukuda , Han Ying, Takahiro Uneo, Masayoshi Soma.
    • Organizer
      15th International SHR Symposium
    • Place of Presentation
      Melbourne, Australia
    • Related Report
      2012 Research-status Report
  • [Presentation] Complement 3 induces renal renin generation through the epitheliao-mesenchymal transition2012

    • Author(s)
      Zhou Xueli, Noboru Fukuda, Takahiro Ueno, Koichi Matsumoto, Masayoshi Soma
    • Organizer
      15th International SHR Symposium
    • Place of Presentation
      Melbourne, Australia
    • Related Report
      2012 Research-status Report
  • [Presentation] C3A-C3A receptor systems is involved in the cardiovascular and renal remodeling’s in hypertensive rats2012

    • Author(s)
      Kazuya Ikeda, Noboru Fukuda, Han Ying, Takahiro Uneo, Akiko Tsunemi, Masayoshi Soma
    • Organizer
      24th Meeting of the International Society of Hypertension
    • Place of Presentation
      Sydney, Australia
    • Related Report
      2012 Research-status Report
  • [Presentation] Complement 3 activates the renal renin-angiotensin system by the epithelial-to-mesenchymal transition2012

    • Author(s)
      Zhou Xueli, Noboru Fukuda, Takahiro Ueno, Koichi Matsumoto, Masayoshi Soma
    • Organizer
      24th Meeting of the International Society of Hypertension
    • Place of Presentation
      Sydney, Australia
    • Related Report
      2012 Research-status Report
  • [Presentation] 補体C3による腎尿細管上皮間葉化(EMT)と腎内レニン-アンジオテンシン(RA)系の活性化2012

    • Author(s)
      Zhou Xueli、福田 昇、上野高浩、松田裕之、西山 成、松本紘一、相馬正義
    • Organizer
      第16回 心血管内分泌代謝学会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 腎尿細管上皮間葉化現象(EMT)による腎内レニン-アンジオテンシン(RA)系活性化―補体C3の関与―2012

    • Author(s)
      Zhou Xueli、福田 昇、上野高浩、遠藤守人、松本紘一、相馬正義、西山 成
    • Organizer
      第3回 腎不全研究会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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