Investigation of molecular mechanism in the development of chronic obstructive pulmonary disease using klotho mutant mice.

• Project/Area Number: 20590893
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Gunma University
• Principal Investigator: SUGA Tatsuo Gunma University, 医学部, 講師 (50334115)
• Co-Investigator(Kenkyū-buntansha): KURABAYASHI Masahiko 群馬大学, 大学院・医学系研究科, 教授 (00215047)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: klotho遺伝子変異マウス / 慢性閉塞性肺疾患(COPD) / Elongation of long-chain fatty acids family member 6 (Elovl6) / 特発性間質性肺炎 / 線維化 / Hypoxia-inducible factor-1α(HIF-1α) / epithelial-mesenchymal transition (EMT) / Notch 1 / 肺気腫 / 石灰化 / HIF-1α / epithelial-mesenchymal transition / Notch / II型肺胞上皮細胞 / アポトーシス / サーファクタント蛋白 / 酸化ストレス / 脂肪酸伸長酵素 / Elov16 / COPD / 分化 / シグナル伝達 / リン代謝 / 遺伝子発現 / 転写因子

Research Abstract

In the klotho mutant mice, osteoblastic transcription factor Runx2 is upregulated in the calcification process. In human emphysema lung, expression of elongation of long-chain fatty acids family member 6 is increased. Hypoxia-inducible factor-1α induces lung fibrosis in mice model. Epithelial-mesenchymal transition through Notch signal pathway plays an important role in fibrogenetic process in mice model and human interstitial pneumonias.

Research Products

• [Journal Article] Hypoxia-inducible factor 1α mediates TGF-β-induced PAI-1 production in alveolar macrophages in pulmonary fibrosis (2011)
  • Author(s): Manabu Ueno
  • Journal Title: Am J Physiol Lung Cell Mol Physiol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Notch Induces Myofibroblast Differentiation of Alveolar Epithelial Cells via Transforming Growth Factor-βSmad3 Pathway (2010)
  • Author(s): Kana Aoyagi-Ikeda
  • Journal Title: Am J Respir Cell Mol Biol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Pioglitazone, a peroxisome proliferator-activated receptor gamma ligand, suppresses bleomycin-induced acute lung injury and fibrosis. (2009)
  • Author(s): Yasuhiro Aoki, Toshitaka Maeno, Kana Aoyagi-Ikeda, Manabu Ueno, Fumiaki Aoki, Nozomi Aoki, Junichi Nakagawa, Yoshichika Sando, Yuji Shimizu, Tatsuo Suga, Masashi Arai, Masahiko Kurabayashi
  • Journal Title: Respiration Vol.77,No.3 Pages: 311-319
  • Peer Reviewed
• [Journal Article] Pioglitazone, a Peroxisome Proliferator-Activated Receptor Gamma Ligand, Suppresses Bleomycin-Induced Lung Injury and Fibrosis (2009)
  • Author(s): Aoki Y
  • Journal Title: Respiration 77(3) Pages: 311-319
  • Peer Reviewed
• [Journal Article] Interleukin-3 does not affect the differentiation of mast cells derived from human bone marrow progenitors. (2008)
  • Author(s): Yuji Shimizu, Kenji Matsumoto, Yoshimichi Okayama, Sakai Kentaro, Toshitaka Maeno, Tatsuo Suga, Toru Miura, Shinji Takai, Masahiko Kurabayashi, Hirohisa Saito
  • Journal Title: Immunol Invest Vol.37,No.1 Pages: 1-17
  • Peer Reviewed
• [Journal Article] Interleukin-3 does not affect the differentiation of mast cells derived from human bone marrow progenitors. (2008)
  • Author(s): Shimizu Y
  • Journal Title: Immunol Invest. 37(1) Pages: 1-17
  • Peer Reviewed
• [Journal Article] Hypoxia-inducible factor-1 α mediates TGF-β -induced PAI-1 production in alveolar macrophages in pulmonary fibrosis.
  • Author(s): Manabu Ueno, Toshitaka Maeno, Miyuki Nomura, Kana Aoyagi-Ikeda, Hiroki Matsui, Kenichiro Hara, Toru Tanaka, Tatsuya Iso, Tatsuo Suga, Masahiko Kurabayashi
  • Journal Title: Am J Physiol Lung Cell Mol Physiol (Epub ahead of print, 2011.)
  • Peer Reviewed
• [Journal Article] Notch induces myofibroblast differentiation of alveolar epithelial cells via transforming growth factor-β-smad3 pathway.
  • Author(s): Kana Aoyagi-Ikeda, Toshitaka Maeno, Hiroki Matsui, Manabu Ueno, Kenichiro Hara, Yasuhiro Aoki, Fumiaki Aoki, Takehisa Shimizu, Hiroshi Doi, Keiko Kawai-Kowase, Tatsuya Iso, Tatsuo Suga, Masashi Arai, Masahiko Kurabayashi
  • Journal Title: Am J Respir Cell Mol Biol (Epub ahead of print, 2010.)
  • Peer Reviewed
• [Presentation] 線維化におけるNotch シグナル経路の役割 (2008)
  • Author(s): 池田香菜、前野敏孝、上野学、濱口重人、磯部全、原健一郎、青木康弘、青木史暁、青木望、磯達也、須賀達夫、倉林正彦
  • Organizer: 第48回日本呼吸器学会総会
  • Place of Presentation: 神戸国際展示場(神戸市)
  • Year and Date: 2008-06-15
• [Presentation] 肺線維化におけるHIF1-αの役割 (2008)
  • Author(s): 上野学、前野敏孝、野村みゆき、青柳香奈、濱口重人、磯部全、原健一郎、青木康弘、青木史暁、青木望、須賀達夫、倉林正彦
  • Organizer: 第48回日本呼吸器学会総会
  • Place of Presentation: 神戸国際展示場(神戸市)
  • Year and Date: 2008-06-15
• [Presentation] 肺線化におけるNotchシグナル経路の役割 (2008)
  • Author(s): 池田香菜
  • Organizer: 第48回日本呼吸器学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2008-06-15
• [Presentation] 肺線化におけるHIF-1αの役割 (2008)
  • Author(s): 上野学
  • Organizer: 第48回日本呼吸器学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2008-06-15
• [Presentation] Role of hypoxia inducible factor-1α in the pathogenesis of pulmonary fibrosis (2008)
  • Author(s): Manabu Ueno, Toshitaka Maeno, Miyuki Nomura, Kana Aoyagi, Shigeto Hamaguchi, Zen Isobe, Kenichiro Hara, Yasuhiro Aoki, Fumiaki Aoki, Nozomi Aoki, Tatsuo Suga, Masahiko Kurabayashi
  • Organizer: 2008 ATS International Cnference
  • Place of Presentation: シェラトンセンタートロントホテル(トロント、カナダ)
  • Year and Date: 2008-05-16
• [Presentation] Role of Hypoxia Inducible Factor-1 α in the Pathogenesis of Pulmonary Fibrosis. (2008)
  • Author(s): Ueno M
  • Organizer: 2008 ATS International Conference
  • Place of Presentation: Canada
  • Year and Date: 2008-05-16