Molecular mechanisms of alveolar epithelial healing process in acute lung injury

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390376
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: University 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
• 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

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.

Research Products

• [Journal Article] Desensitization by different strategies of epidermal growth factor receptor and ErbB4 (2014)
  • 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
  • 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
  • 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): 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
  • 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 mechanism (2013)
  • 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
  • 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(11) Pages: 1163-4
  • 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
  • Peer Reviewed
• [Journal Article] Latest evidence in endothelium-derived hyperpolarizing factor research (2012)
  • Author(s): Masato Tsutsui, Yusuke Ohya, Kazuhiro Sugahara
  • Journal Title: Circulation Journal Volume: 76 (7) Pages: 1599-1600
  • Peer Reviewed
• [Journal Article] Induction of epithelial-mesenchymal transition by flagellin in cultured lung epithelial cells (2012)
  • 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 Pages: L1057-L1069
  • Peer Reviewed
• [Journal Article] Interaction of ethyl pyruvate in vitro with NF-kB subunits (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Increasing dihydrobiopterin causes dysfunction of endothelial nitric oxide synthase in rats in vivo (2011)
  • 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) Pages: H721-9
  • 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 paraplegia (2011)
  • 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
  • Peer Reviewed
• [Presentation] The efficiency of skill training for medical students in the clinical training of anesthesiology (2014)
  • Author(s): H. Nishi, J. Okubo, M. Kakinohana, K. Sugahara
  • Organizer: 2014 WGEA, AAMC Western regional conference
  • Place of Presentation: Univ Hawaii
  • Year and Date: 20140323-25
• [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, U.S.A.
  • Year and Date: 20131012-16
• [Presentation] A new model of global cerebral ischemia in mice (2013)
  • 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
  • Year and Date: 20131012-16
• [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, U.S.A
  • Year and Date: 20131012-16
• [Presentation] Anesthetic 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, U.S.A
  • Year and Date: 20131012-16
• [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
  • Year and Date: 20130517-22
• [Presentation] Availability of initial distribution volume of glucose (IDVG) for the volume control in pulmonary decompression illness (2013)
  • 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
  • Year and Date: 20130504-07
• [Presentation] Dihydrobiopterin causes endothelial nitric oxide synthase dysfunction in rats in vivo (2012)
  • 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
  • Year and Date: 20121103-07
• [Presentation] Surgical apgar score can predict postoperative complications in nonagenarian patients (2012)
  • 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
  • Year and Date: 20121013-17
• [Presentation] Expression of D-serine in the spinal cord after transient ischemia in mice (2012)
  • 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
  • Year and Date: 20121011-12
• [Presentation] Application of inhaled anesthesia induction and maintenance in patients with difficult airway (2011)
  • Author(s): Kazuhiro Sugahara
  • Organizer: The Chinese Society of Anesthesiology (CSA) 2011 Annual meeting
  • Place of Presentation: Shandong Hotel, Ji'nan, Chin
  • Year and Date: 20110909-10
  • Invited
• [Presentation] Ethyl pyruvate inhibited the nuclear translocation of NF-kB through interaction with RelA and P50 in cultured lung epithelial cells (2011)
  • Author(s): K. Sugahara, A. Mizutani, H. Yamamoto
  • Organizer: 2011 International conference of American Thoracic Society
  • Place of Presentation: Denver, Colorado, U.S.A
  • Year and Date: 20110513-18
• [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(190-194)
  • Publisher: 中山書店
• [Book] 心臓麻酔における臓器保護 (2013)
  • Author(s): 澄川耕二
  • Total Pages: 283(116-121)
  • Publisher: 総合医学社