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Molecular mechanisms of alveolar epithelial healing process in acute lung injury

Research Project

Project/Area Number 23390376
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionUniversity of the Ryukyus

Principal Investigator

SUGAHARA Kazuhiro  琉球大学, 医学(系)研究科(研究院), 教授 (20171126)

Co-Investigator(Kenkyū-buntansha) OSHIRO Masakatsu  琉球大学, 医学部附属病院, 助教 (00315483)
TERUYA Koji  琉球大学, 大学院・医学研究科, 助教 (50437985)
MIYATA Yuji  琉球大学, 医学部附属病院, 講師 (60315471)
NOGUCHI Nobuhiro  琉球大学, 医学部附属病院, 助教 (80457671)
IZUMI Syunsuke  琉球大学, 医学部附属病院, 助教 (90649401)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2013: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2011: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords急性肺傷害 / 創傷治癒 / 肺胞上皮細胞 / 細胞増殖因子 / EGFR / サイトカイン / NF-kB / EMT / エチルピルビン酸 / epithelial-mesenchymal transition
Research Abstract

1. We have demonstrated that 1) keratinocyte growth factor (KGF) is a potent factor for proliferation and differentiation of alveolar type II cells, 2) intratracheal instillation of KGF prevented acute lung injury by bleomycin and HCl. 2. Ethyl pyruvate reportedly has anti-inflammatory actions through inhibition of NF-kB. We confirmed that treatment of cultured alveolar epithelial cells with tumor necrosis factor a (TNFa) increased the NF-kB/DNA-binding activity, which was strongly inhibited with incubating with ethyl pyruvate. We also demonstrated that ethyl pyruvate interacts with RelA and p50 to inhibit their functions at multiple points. 3. Legionella pneumophila has flagella, causes pulmonary fibrosis. Microarray analysis in cultured alveolar epithelial cells indicated that flagellin increased fibronectin level and reduced E-cadherin level, which suggested that flagellin cooperates with TGF-b and induces EMT in alveolar epithelial cells, and causes fibrosis.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (47 results)

All 2014 2013 2012 2011

All Journal Article (22 results) (of which Peer Reviewed: 22 results) Presentation (21 results) (of which Invited: 1 results) Book (4 results)

  • [Journal Article] Desensitization by different strategies of epidermal growth factor receptor and ErbB42014

    • Author(s)
      Hideyuki Yamamoto, Sayomi Higa-Nakamine, Nobuhiro Noguchi, Noriko Maeda, Yutaka Kondo, Seikichi Toku, Ichiro Kukita, Kazuhiro Sugahara
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 124 Pages: 287-293

    • NAID

      130003391497

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 特集エビデンスに基づいた周術期の安全管理, 術中クライシスと外科的アプガースコア2014

    • Author(s)
      大城匡勝, 須加原一博
    • Journal Title

      麻酔

      Volume: 63 Pages: 262-268

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Desensitization by Different Strategies of Epidermal Growth Factor Receptor and ErbB42014

    • Author(s)
      H Yamamoto, S Higa-Nakamine, N Noguchi, N Maeda, Y Kondo, S Toku, I Kukita, K Sugahara
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 124 Issue: 3 Pages: 287-293

    • DOI

      10.1254/jphs.13R11CP

    • NAID

      130003391497

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of epidermal growth factor receptor at serine 1047 by MAP kinase-activated protein kinase-2 in cultured lung epithelial cells treated with flagellin2013

    • Author(s)
      Nobuhiro Noguchi, Yutaka Kondo, Noriko Maeda, Sayomi Higa-Nakamine, Seikichi Toku, Junichi Maruyama, Yoichiro Isohama, Ichiro Kukita, Kazuhiro Sugahara, Hideyuki Yamamoto
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 529 Pages: 75-85

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Long-term treatment with San'o-shashin-to, Kampo medicine, markedly ameliorates cardiac ischemia-reperfusion injury in ovariectomized rats via the Redox-dependent mechanism2013

    • Author(s)
      Mayuko Sakanashi, T. Matsuzaki, K. Noguchi, J. Nakasone, M. Sakanashi, T. Uchida, M. Kina-Tanada, H. Kubita, K. Arakaki, A. Tanimoto, N. Yanagihara, M. Sakanashi, Y. Ohya, H. Masuzaki, S. Ishiuchi, K. Sugahara, M. Tsutsui
    • Journal Title

      Circulation Journal

      Volume: 77 (7) Pages: 1827-1837

    • NAID

      10031173765

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Obstacle of guide wire advancement by the internal jugular vein valve with opening restriction : An ultrasound image2013

    • Author(s)
      T. Tadokoro, K. Yoza, K. Sugahara
    • Journal Title

      Canadian Journal of Anesthesia

      Volume: 60(11) Pages: 1163-4

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dihydrobiopterin による内皮型一酸化窒素合成酵素機能障害2013

    • Author(s)
      野口克彦, 濱舘直史, 松崎俊博, 坂梨まゆ子, 仲宗根淳子, 内田太郎, 新垣久美子, 久保田陽秋, 石内勝吾, 益崎裕章, 須加原一博, 大屋祐輔, 坂梨又郎, 筒井正人
    • Journal Title

      Ryukyu Med J

      Volume: 32(1, 2) Pages: 7-12

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of epidermal growth factor receptor at serine 1047 by MAP kinase-activated protein kinase-2 in cultured lung epithelial cells treated with flagellin.2013

    • Author(s)
      N Noguchi, Y Kondo, N Maeda, S Higa-Nakamine, S Toku, J Maruyama, Y Isohama, I Kukita, K Sugahara, H Yamamoto
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 529 Issue: 2 Pages: 75-85

    • DOI

      10.1016/j.abb.2012.11.006

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-Term Treatment With San’o-Shashin-To, a Kampo Medicine, Markedly Ameliorates Cardiac Ischemia-Reperfusion Injury in Ovariectomized Rats via the Redox-Dependent Mechanism2013

    • Author(s)
      Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Sakanashi M, Uchida T, Kina-Tanada M, Kubota H, Arakaki K, Tanimoto A, Yanagihara N, Sakanashi M, Ohya Y, Masuzaki H, Ishiuchi S, Sugahara K, Tsutsui M
    • Journal Title

      Circulation Journal

      Volume: 77 Issue: 7 Pages: 1827-1837

    • DOI

      10.1253/circj.CJ-12-1434

    • NAID

      10031173765

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Obstacle of guide wire advancement by the internal jugular vein valve with opening restriction: An ultrasound image.2013

    • Author(s)
      T Tadokoro, K Yoza, K Sugahara
    • Journal Title

      Canadian Journal of Anesthesia

      Volume: 60 Issue: 11 Pages: 1163-1164

    • DOI

      10.1007/s12630-013-0022-8

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dihydrobiopterinによる内皮型一酸化窒素合成酵素機能障害2013

    • Author(s)
      野口克彦、濱舘直史、松崎俊博、坂梨まゆ子、仲宗根淳子、内田太郎、新垣久美、久保田陽秋、石内勝吾、益崎裕章、須加原一博、大屋祐輔、坂梨又郎、筒井正人
    • Journal Title

      Ryukyu Medical Journal

      Volume: 32 Pages: 7-12

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Latest evidence in endothelium-derived hyperpolarizing factor research.2013

    • Author(s)
      TsuTsui, M., et al.
    • Journal Title

      Circulation Journal

      Volume: 76 (7) Pages: 1599-1600

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of epidermal growth factor at serine 1047 by MAP kinase-activated protein kinase-2 in cultured lung epithelial cells treated with flagellin2013

    • Author(s)
      Noguchi, N., et al.
    • Journal Title

      Archieves of Biochemistry & Biophysics

      Volume: 529 Pages: 75-85

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Latest evidence in endothelium-derived hyperpolarizing factor research2012

    • Author(s)
      Masato Tsutsui, Yusuke Ohya, Kazuhiro Sugahara
    • Journal Title

      Circulation Journal

      Volume: 76 (7) Pages: 1599-1600

    • NAID

      10030503134

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induction of epithelial-mesenchymal transition by flagellin in cultured lung epithelial cells2012

    • Author(s)
      Yutaka Kondo, Sayomi Higa-Nakamine, Nobuhiro Noguchi, Noriko Maeda, Seikichi Toku, Yoichiro Isohama, Kazuhiro Sugahara, Ichiro Kukita, Hideyuki Yamamoto
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol

      Volume: 303

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induction of epithelial-mesenchymal transition by flagellin in cultured lung epithelial cells.2012

    • Author(s)
      Kondo, Y., et al.
    • Journal Title

      American Journal of Physiology Lung Cell Molecular Physiology

      Volume: 303

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interaction of ethyl pyruvate in vitro with NF-kB subunits2011

    • Author(s)
      Ayako Mizutani, Noriko Maeda, Seikichi Toku, Sayomi Higa-Nakamine, Yoichiro, Isohama, Hajime Sunakawa, Kazuhiro Sugahara, Hideyuki Yamamoto
    • Journal Title

      RelA and p50 European Journal of Pharmacology

      Volume: 650 (1) Pages: 151-156

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increasing dihydrobiopterin causes dysfunction of endothelial nitric oxide synthase in rats in vivo2011

    • Author(s)
      Noguchi K, Hamadate N, Matsuzaki, T, Sakanashi M, Nakasone J, Arakaki K, Kubota H, Sugahara K, Ohya Y, Sakanashi M, Tsutsui M
    • Journal Title

      Am J Physiol Heart Circ Physiol

      Volume: 301 (3)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Potent suppression of stretch reflex activity after systemic or spinal delivery of tizanidine in rats with spinal ischemia-induced chronic spastic paraplegia2011

    • Author(s)
      T. Fuchigami, O. Kakinohana, MP Hefferan, N Lukacova, S Marsala, O Platoshyn, K Sugahara, TL Yaksh, M Marsala
    • Journal Title

      Neuroscience

      Volume: 194 Pages: 160-169

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interaction of ethyl pyruvate in vitro with NF-kB subunits, RelA and p502011

    • Author(s)
      Mizutani A, et al
    • Journal Title

      British Journal of Pharmacology

      Volume: 650(1) Pages: 151-156

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increasing dihydrobiopterin causes dysfunction of endothelial nitric oxide synthase in ratss in vitro2011

    • Author(s)
      Noguchi K, et al
    • Journal Title

      American Journal of Physiology -Heart and Circulatory Physiology

      Volume: 301(3)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potent suppression of strech reflex activity after systemic or spinal delivery of tizanidine in rats with spinal ischemia-induced chronic spastic2011

    • Author(s)
      Fuchigami T, et al
    • Journal Title

      Neuroscience

      Volume: 194 Pages: 160-169

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] The efficiency of skill training for medical students in the clinical training of anesthesiology2014

    • Author(s)
      H. Nishi, J. Okubo, M. Kakinohana, K. Sugahara
    • Organizer
      2014 WGEA, AAMC Western regional conference
    • Place of Presentation
      Univ Hawaii
    • Related Report
      2013 Final Research Report
  • [Presentation] Noradrenaline does not impair postoperative renal function in endovascular stent graft repair2013

    • Author(s)
      T. Kinjo, Y. Madanbashi, S. Izumi, M. Oshiro, K. Sugahara
    • Organizer
      2013 annual meeting of American Society of the Anesthesiologists
    • Place of Presentation
      San Francisco, U.S.A.
    • Related Report
      2013 Final Research Report
  • [Presentation] A new model of global cerebral ischemia in mice2013

    • Author(s)
      T. Fukuda, S. Iseki, M. Kakinohana, C. Takayama, M. Matsushita, K. Sugahara
    • Organizer
      2013 annual meeting of American Society of Anesthesiologists
    • Place of Presentation
      San Francisco, U.S.A
    • Related Report
      2013 Final Research Report
  • [Presentation] Skeletal muscle mass serves as an index of a neuromuscular junction blocking agent does2013

    • Author(s)
      H. Nishi, K. Kitano, S. Taira, M. Kakinohana, K. Sugahara
    • Organizer
      2013 annual meeting of American Society of the Anesthesiologists
    • Place of Presentation
      San Francisco, U.S.A
    • Related Report
      2013 Final Research Report
  • [Presentation] Anesthetic management in an adult patient with double-chambered right ventricle and severe obesity2013

    • Author(s)
      T.Tadokoro, H. Higa, T. Kawabata, K. Yoza, M. Kakinohana, K. Sugahara
    • Organizer
      2013 annual meeting of American Society of the Anesthesiologists
    • Place of Presentation
      San Francisco, U.S.A
    • Related Report
      2013 Final Research Report
  • [Presentation] Stem cell progenitor cells : Promising future strategies in repair, Thematic Poster Session [A89]2013

    • Author(s)
      V.N. Lama, K. Sugahara, R. Sehmi
    • Organizer
      American Thoracic Society (ATS) 2013 International Conference
    • Place of Presentation
      Philadelphia, Pennsylvania, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Availability of initial distribution volume of glucose (IDVG) for the volume control in pulmonary decompression illness2013

    • Author(s)
      K. Aragaki, K. Kamizato, T. Fuchigami, T. Teruya, M. Kakinohana, K. Sugahara
    • Organizer
      "The chokes" International Anesthesia Research Society (IARS) 2013 annual meeting
    • Place of Presentation
      San Diego, California, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Availability of initial distribution volume of glucose (IDVG) for the volume control in pulmonary decompression illness; "The chokes"2013

    • Author(s)
      K Aragaki, K Kamizato, T Fuchigami, T Teruya, M Kakinohana, K Sugahara
    • Organizer
      International Anesthesia Research Society (IARS) 2013
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Noradrenaline does not impair postoperative renal function in endovascular stent graft repair.2013

    • Author(s)
      T Kinjo, Y Madanbashi, S Izumi, M Oshiro, K Sugahara
    • Organizer
      2013 annual meeting of American Society of the Anesthesiologists
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] A new model of global cerebral ischemia in mice.2013

    • Author(s)
      T Fukuda, S Iseki, M Kakinohama, C Takayama, M Matsushita, K Sugahara
    • Organizer
      2013 annual meeting of American Society of the Anesthesiologists
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Skeletal muscle mass serves as an index of a neuromuscular junction blocking agent does.2013

    • Author(s)
      H Nishi, K Kitano, S Taira, M Kakinohana, K Sugahara
    • Organizer
      2013 annual meeting of American Society of the Anesthesiologists
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Snesthetic management in an adult patient with double-chambered right ventricle and severe obesity.2013

    • Author(s)
      T Tadokoro, H Higa, T Kawabata, K Yoza, M Kakinohana, K Sugahara
    • Organizer
      2013 annual meeting of American Society of the Anesthesiologists
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Dihydrobiopterin causes endothelial nitric oxide synthase dysfunction in rats in vivo2012

    • Author(s)
      M Tsutsui, K Noguchi, T Matsuzaki, M Sakanashi, J Nakasone, T Uchida, M Tanada, H Kubota, K Sugahara, Y Ohya
    • Organizer
      Annual meeting of AHA Scientific Sessions
    • Place of Presentation
      Los Angels, California, U.S.A
    • Related Report
      2013 Final Research Report
  • [Presentation] Surgical apgar score can predict postoperative complications in nonagenarian patients2012

    • Author(s)
      R. Kakihana, M. Abe, N. Noguchi, M. Oshiro, K. Sugahara
    • Organizer
      2012 annual meeting of American Society of the Anesthesiologists
    • Place of Presentation
      Washington DC, U.S.A
    • Related Report
      2013 Final Research Report
  • [Presentation] Expression of D-serine in the spinal cord after transient ischemia in mice2012

    • Author(s)
      M. Kakinohana, K. Kamizato, S. Iseki, T. Fukuda, K. Sugahara
    • Organizer
      40th annual meeting of Society for neuroscience in anesthesiology and critical care
    • Place of Presentation
      Washington DC
    • Related Report
      2013 Final Research Report
  • [Presentation] Surgical apgar score can predict postoperative comlications in nonagenarian patients.2012

    • Author(s)
      Kakinohana R, et al.
    • Organizer
      American Society of the Anesthesiologist
    • Place of Presentation
      Washington, DC, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Expression of D-serine in the spinal cord after transient ischemia in mice.2012

    • Author(s)
      Kakinohana, M., et al.
    • Organizer
      40th annual meeting of Society for neuroscience in anesthesiology and critical care
    • Place of Presentation
      Washington, DC, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Dihydrobiopterin causes endothelial nitric oxide synthase dysfunction in rats in vivo.2012

    • Author(s)
      Tsutsui, M., et al.
    • Organizer
      Annual meeting of AHA Scientific Sessions
    • Place of Presentation
      Los Angels, CA, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Ethyl pyruvate inhibited the nuclear translocation of NF-kB through interaction with RelA and P50 in cultured lung epithelial cells2011

    • Author(s)
      K. Sugahara, A. Mizutani, H. Yamamoto
    • Organizer
      2011 International conference of American Thoracic Society
    • Place of Presentation
      Denver, Colorado, U.S.A
    • Related Report
      2013 Final Research Report
  • [Presentation] Application of inhaled anesthesia induction and maintenance in patients with difficult airway2011

    • Author(s)
      Kazuhiro Sugahara
    • Organizer
      The Chinese Society of Anesthesiology (CSA) 2011 Annual meeting
    • Place of Presentation
      Shandong Hotel, Ji'nan, Chin
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Ethyl pyruvate inhibited the nuclear translocation of NF-kB through interaction with RelA and p50 in cultured lung epithelial cells2011

    • Author(s)
      Sugahara K, et al
    • Organizer
      2011 International conference of American Thoracic Society
    • Place of Presentation
      Denver, Colorado, U.S.A.
    • Related Report
      2011 Annual Research Report
  • [Book] 麻酔科医のための周術期の疼痛管理2014

    • Author(s)
      森田 潔
    • Total Pages
      305
    • Publisher
      中山書店
    • Related Report
      2013 Final Research Report
  • [Book] 麻酔科医のための周術期の疼痛管理2014

    • Author(s)
      川真田樹人編集、森田潔監修
    • Total Pages
      305
    • Publisher
      中山書店
    • Related Report
      2013 Annual Research Report
  • [Book] 心臓麻酔における臓器保護2013

    • Author(s)
      澄川耕二
    • Total Pages
      283
    • Publisher
      総合医学社
    • Related Report
      2013 Final Research Report
  • [Book] 徹底ガイド 心臓麻酔Q&A2013

    • Author(s)
      澄川耕二編集
    • Total Pages
      283
    • Publisher
      総合医学社
    • Related Report
      2013 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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