Effects of hepatocyte growth factor in the mechanism of airway hyperresponsiveness,inflammation and remodeling

• Project/Area Number: 17607007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: アレルギー
• Research Institution: Okayama University
• Principal Investigator: KANEHIRO Arihiko Okayama University, 医学部・歯学部附属病院, 講師 (20243503)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
• Keywords: HGF / 気管支喘息 / マウス喘息モデル / 気道リモデリング / 再生医療 / 気道炎症 / 遺伝子治療

Research Abstract

今回の気管支喘息の発症・難治化における肝細胞増殖因子(hepatocyte growth factor ; HGF)の研究において、喘息発症モデル及び気道リモデリングモデルを作製後、リコンビナントHGF及び抗HGF抗体を投与し気道炎症、気道過敏性、Th2サイトカインやTGF-β等の増殖因子さらに気道上皮細胞、上皮下平滑筋や線維性変化を検討した。その結果、HGFがアレルギ-性気道炎症、気道過敏性の抑制効果のみでなく、すでに形成された気道リモデリングに対しても抑制的に制御することが明らかとなり、HGFは今後極めて有用な重症難治性喘息治療薬として期待される

Research Products

• [Journal Article] Hepatocyte growth factor suppresses production of reactiveoxygen species and release of eosinophil-derived neurotoxin from human eosinophils (2008)
  • Author(s): Ito W, Kanehiro A, (他9名、7番目)
  • Journal Title: Int Arch Allegy Immunol 147 Pages: 331-337
  • Peer Reviewed
• [Journal Article] Anti-allergic inflammatory effects of hepatocyte growth factor (2008)
  • Author(s): Ito W, Kanehiro A, (他9名、9番目)
  • Journal Title: Int Arch Allergy Immunol 146 Pages: 82-87
  • Peer Reviewed
• [Journal Article] Inflammatory markers in exhaled breath condensate from patients with asthma (2008)
  • Author(s): Ueno T, Kanehiro A, (他8名、6番目)
  • Journal Title: Respirology 5 Pages: 654-663
  • Peer Reviewed
• [Journal Article] Growth factors temporally associate with airway responsiveness and inflammation in allergen-exposed mice (2008)
  • Author(s): Ito W, Kanehiro A, (他13名、5番目)
  • Journal Title: Int Arch Allergy Immunol 145 Pages: 324-339
  • Peer Reviewed
• [Journal Article] Whole blood interferon-gamma assay for baseline tuberculosis screening among Japanese healthcare students (2008)
  • Author(s): Hotta K, Kanehiro A, (他8名、7番目)
  • Journal Title: PLoS ONE 2
  • Peer Reviewed
• [Journal Article] Growth factors temporally associate with airway responsiveness andinflammation in allergen-exposed mice (2008)
  • Author(s): Ito W, Kanehiro A
  • Journal Title: Int Arch Allergy Immunol 145 Pages: 324-339
  • Peer Reviewed
• [Journal Article] Anti-allergic inflammatory effects of hepatocyte growth factor (2008)
  • Author(s): Ito W, Kanehiro A
  • Journal Title: Int Arch Allergy Immunol 146 Pages: 82-87
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor suppresses production of reactive oxygen species and release of eosinophil-derived neurotoxin from human eosinophils (2008)
  • Author(s): Ito W, Kanehiro A
  • Journal Title: Int Arch Allergy Immunol 147 Pages: 331-337
  • Peer Reviewed
• [Journal Article] Growth factors temporally associate with airway responsiveness and inflammation in allergen-exposed mice (2008)
  • Author(s): Ito W, Kanehiro A
  • Journal Title: Int Arch Allergy Immunol 145 Pages: 324-339
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor attenuates eotaxin and PGD2-induced chemotaxis of human eosinophils (2007)
  • Author(s): Ito W, Kanehiro A, (他5名、3番目)
  • Journal Title: Allergy 62 Pages: 412-420
  • Peer Reviewed
• [Journal Article] Elevated serum level of siaylated glycoprotein KL-6 predicts a poor prognosis in patients with non-small cell lung cancer treated with gefitinib (2007)
  • Author(s): Fujiwara Y, Kanehiro A, (他10名、9番目)
  • Journal Title: Lung Cancer 59 Pages: 81-87
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor attenuates eotaxin and PGD2-induced chemotaxis of human eosinophils (2007)
  • Author(s): Ito W, Kanehiro A
  • Journal Title: Allergy 62 Pages: 415-420
  • Peer Reviewed
• [Journal Article] Severe interstitial pneumonia induced by paclitaxel in a patient with adenocarcinoma of the lung (2006)
  • Author(s): Suzaki N, Kanehiro A, (他8名、8番目)
  • Journal Title: Acta Med Okayama 60 Pages: 295-298
  • Peer Reviewed
• [Journal Article] Pirfenidone modulates airway responsiveness, inflammation and remodeling after repeated challenge (2006)
  • Author(s): Hirano A, Kanehiro A, (他9名、2番目)
  • Journal Title: Am J Respir Cell Mol Biol 35 Pages: 366-377
  • Peer Reviewed
• [Journal Article] 気道リモデリングの制御とHGF (2006)
  • Author(s): 伊藤亘, 金廣有彦
  • Journal Title: 臨床免疫 45 Pages: 64-69
• [Journal Article] 気道リモデリングにおけるHGFの役割と効果 (2006)
  • Author(s): 伊藤亘, 金廣有彦
  • Journal Title: アレルギー科 21 Pages: 557-565
• [Journal Article] 気管支喘息と増殖因子.HGF (2006)
  • Author(s): 金廣有彦
  • Journal Title: 細胞増殖因子と再生医療(メディカルレビュ-社)
• [Journal Article] 気道リモデリングにおけるHGFの役割と効果 (2006)
  • Author(s): 伊藤亘, 金廣有彦
  • Journal Title: アレルギ-科 21 Pages: 557-565
• [Journal Article] Interstitial lung disease in Japanese patients with non-small cell lung cancer receiving gefitinib : an analysis of risk factors and treatment outcomes in Okayama Lung Cancer Study Group (2005)
  • Author(s): Hotta K, Kanehiro A, (他15名、13番目)
  • Journal Title: Cancer J 11 Pages: 417-424
  • Peer Reviewed
• [Journal Article] Systemic tumor embolism mimicking gefitinib-induced interstitial lung disease in a patientwith lung cancer (2005)
  • Author(s): Umemura S, Kanehiro A, (他9名、8番目)
  • Journal Title: Intern Med 44 Pages: 979-982
  • Peer Reviewed
• [Journal Article] Sarcoidosis occurring after interferon-alpha therapy for chronic hepatitis C : report of two cases (2005)
  • Author(s): Hirano A, Kanehiro A, (他8名、9番目)
  • Journal Title: Respirology 10 Pages: 529-534
  • Peer Reviewed
• [Journal Article] Successful treatment of pulmonary arterysarcoma by a two-drug combination chemotherapy consisting of ifosfamide and epirubicin (2005)
  • Author(s): Uchida A, Kanehiro A, (他7名、5番目)
  • Journal Title: Jpn J Clin Oncol 35 Pages: 417-419
  • Peer Reviewed
• [Journal Article] Airway hyperresponsiveness in the absence of CD4+ T Cells after primary but not secondary challenge (2005)
  • Author(s): Joetham A, Kanehiro A, (他5名、5番目)
  • Journal Title: Am J Respir Cell Mol Biol 33 Pages: 89-96
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor attenuates airway hyper responsiveness, inflammation and remodeling (2005)
  • Author(s): Ito W, Kanehiro A, (他8名、2番目)
  • Journal Title: Am J Respir Cell Mol Biol 32 Pages: 268-280
  • Peer Reviewed
• [Journal Article] Alteration of airway sensory neuropeptide expression and development of airway hyperresponsiveness following respiratory syncytial virus infection (2005)
  • Author(s): Dakhama A,Kanhio A, (他11名、8番目)
  • Journal Title: Am J hysiol Lung Cell Mol Physiol 288
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor attenuates airway hyperresponsiveness, inflammation and remodeling (2005)
  • Author(s): Ito W, Kanehiro A
  • Journal Title: Am J Respir Cell Mol Biol 32 Pages: 268-280
• [Presentation] Hepatocyte Growth factors attenuates production of reactive oxygen species and release of eosinophil-derived neutrotoxine from human eosinpphils (2008)
  • Author(s): Ito W, Kanehiro A
  • Organizer: American Thoracic Society International Conference 2008
  • Place of Presentation: Toronto
  • Year and Date: 2008-05-20
• [Presentation] Growth factors temporally associate with airway inflammation and responsiveness inOvalbumin-sensitized mice (2007)
  • Author(s): Ito W, Kanehiro A
  • Organizer: American Thoracic Society International Conference2007
  • Place of Presentation: San Francisco
  • Year and Date: 2007-05-23
• [Presentation] Growth factors temporally associate with airway inflammation and responsiveness in Ovalbumin-sensitized mice (2007)
  • Author(s): Ito W, Kanehiro A
  • Organizer: American Thoracic Society International Conference 2007
  • Place of Presentation: San Francisco
  • Year and Date: 2007-05-23
• [Presentation] Hepatocyte growth factor attenuates eosinophil chemotaxis (2006)
  • Author(s): Ito W, Kanehiro A
  • Organizer: American Thoracic Society International Conference 2006
  • Place of Presentation: San Diego
  • Year and Date: 2006-05-23
• [Book] 細胞増殖因子と再生医療 (2006)
  • Author(s): 金廣有彦
  • Publisher: メディカルレビュー社気管支喘息と増殖因子.HGF
• [Patent(Industrial Property Rights)] Asthma Preparation. A preventive or therapeutic agent for asthma, comprising HGF or its salt as an active ingredient(金廣有彦、谷本光音、伊藤 亘、松本邦夫、中村敏一. 同左) (2007)
  • Filing Date: 2007
  • Overseas
• [Patent(Industrial Property Rights)] Asthma Preparation. A preventive or therapeutic agent for asthma, comprising HGF or its salt as an active ingredinet (2007)
  • Inventor(s): 金廣有彦、谷本 光音、伊藤 亘、松本邦夫、中村敏一
  • Industrial Property Rights Holder: 金廣有彦、谷本 光音、伊藤 亘、松本邦夫、中村敏一
  • Filing Date: 2007
  • Overseas