Decrease of type II pneumocyte function by aging in the process oflung fibrosis : multi-aspect evaluation of STAM1 gene

• Project/Area Number: 19390223
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tohoku University
• Principal Investigator: NUKIWA Toshihiro Tohoku University, 大学院・医学系研究科, 教授 (40129036)
• Co-Investigator(Kenkyū-buntansha): EBINA Masahito 東北大学, 大学院・医学系研究科, 准教授 (10280885) ; 田澤 立之 東北大学, 病院, 助教 (70301041) ; 兼平 雅彦 東北大学, 加齢医学研究所, 研究員 (90374941) ; 田中 伸幸 東北大学, 宮城県立がんセンター, 部長 (60280872)
• Co-Investigator(Renkei-kenkyūsha): TAZAWA Ryushi 新潟大学, 医歯学総合病院, 講師 (70301041) ; KANEHIRA Masahiko 東北大学, 加齢医学研究所, 技術補佐 (90374941) ; TANAKA Nobuyuki 宮城県県立がんセンター, 部長 (60280872) ; HISATA Shu 東北大学, 高等教育開発推進センター, 助教 (60466571)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2008: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2007: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
• Keywords: 肺線維症 / 加齢変化 / DNAメチル化 / STAM1遺伝子 / II型肺胞上皮細胞

Research Abstract

肺線維症は高齢者を中心とする、進行性の予後不良な肺疾患である。本研究は本病態形成に関与する遺伝子として、アダプター蛋白として細胞内輸送に関与するSTAM1遺伝子に着目し、総合的に検討した。その結果、末梢血細胞のSTAM1遺伝子mRNAは肺線維症患者で発現低下をみた。しかし、STAM1の上流CpG領域のDNAメチル化を詳細に検討したが、健常者との差はなかった。最近、本病態関連遺伝子としてテロメレース遺伝子が報告された。

Research Products

• [Journal Article] Inhaled Granulocyte/Macrophage-Colony Stimulating Factor as Therapy of Pulmonary Alveolar Proteinosis (2010)
  • Author(s): Tazawa R, Trapnell BC, Inoue Y, Arai T, Takada T, Nasuhara Y, Hizawa N, Kasahara Y, Tatsumi K, Hojo M, Ishii H, Yokoba M, Tanaka N, Yamaguchi E, Eda R, Tsuchihashi Y, Morimoto K, Akira M, Terada M, Otsuka J, Ebina M, Kaneko C, Nukiwa T, Krischer JP, Akazawa K, Nakata K.
  • Journal Title: Am J Respir Crit Care Med. (in press)
  • Peer Reviewed
• [Journal Article] Serial OX40 engagement on CD4+ T cells and natural killer T cells causes allergic airway inflammation (2010)
  • Author(s): Damayanti T, Kikuchi T, Zaini J, Daito H, Kanehira M, Kohu K, Ishii N, Satake M, Sugamura K, Nukiwa T.
  • Journal Title: Am J Respir Crit Care Med. (in press)
  • Peer Reviewed
• [Journal Article] Pirfenidone in idiopathic pulmonary fibrosis (2010)
  • Author(s): Taniguchi H, Ebina M, Kondoh Y, Ogura T, Azuma A, Suga M, Taguchi Y, Takahashi H, Nakata K, Sato A, Takeuchi M, Raghu G, Kudoh S, Nukiwa T, Pirfenidone Clinical Study Group in Japan
  • Journal Title: Eur Respir J. (in press)
  • Peer Reviewed
• [Journal Article] Therapeutic effect of lecithinized superoxide dismutase on bleomycin-induced pulmonary fibrosis (2010)
  • Author(s): Tanaka K, Ishihara T, Azuma A, Kudoh S, Ebina M, Nukiwa T, Sugiyama Y, Tasaka Y, Namba T, Ishihara T, Sato K, Mizushima Y, Mizushima T.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol 298(3)
  • Peer Reviewed
• [Journal Article] Pirfenidone in idiopathic pulmonary fibrosis (2010)
  • Author(s): Taniguchi H, Ebina M, Kondoh H, et al
  • Journal Title: Eur Respir J 35 Pages: 821-829
  • Peer Reviewed
• [Journal Article] Therapeutic effect of lecitinized superoxide dismutase on bleomycin-induced pulmonary fibrosis (2010)
  • Author(s): Tanaka K, Ishihara T, Azuma A, et al
  • Journal Title: Am J Physiol Lung Cell Mol Physiol 298
  • Peer Reviewed
• [Journal Article] A genome-wide association study identifies an association of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis (2008)
  • Author(s): Mushiroda T, Wattanapokayakit S, Takahashi A, Nukiwa T, Kudoh S, Ogura T, Taniguchi H, Kubo M, Kamatani N, Nakamura Y, Pirfenidone Clinical Study Group
  • Journal Title: J Med Genet. 45(10) Pages: 654-656
  • Peer Reviewed
• [Journal Article] Suppression of surfactant protein A by an epidermal growth factor receptor tyrosine kinase inhibitor exacerbates lung inflammation (2008)
  • Author(s): Inoue A, Xin H, Suzuki T, Kanehira M, Kuroki Y, Fukuhara T, Kikuchi T, Maemondo M, Nukiwa T, Saijo Y.
  • Journal Title: Cancer Sci. 99(8) Pages: 1679-1684
  • NAID: 10024010194
  • Peer Reviewed
• [Journal Article] Secretory leukocyte peptidase inhibitor and lung cancer (2008)
  • Author(s): Nukiwa T, Suzuki T, Fukuhara T, Kikuchi T.
  • Journal Title: Cancer Sci. 99(5) Pages: 849-855
  • NAID: 10024005504
  • Peer Reviewed
• [Journal Article] Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan (2008)
  • Author(s): Inoue Y, Trapnell BC, Tazawa R, Arai T, Takada T, Hizawa N, Kasahara Y, Tatsumi K, Hojo M, Ichiwata T, Tanaka N, Yamaguchi E, Eda R, Oishi K, Tsuchihashi Y, Kaneko C, Nukiwa T, Sakatani M, Krischer JP, Nakata K, Japanese Center of the Rare Lung Diseases Consortium
  • Journal Title: Am J Respir Crit Care Med. 177(7) Pages: 752-762
  • Peer Reviewed
• [Journal Article] Epidemiology of sarcoidosis in Japan (2008)
  • Author(s): Morimoto T, Azuma A, Abe S, Usuki J, Kudoh S, Sugisaki K, Oritsu M, Nukiwa T.
  • Journal Title: Eur Respir J. 31(2) Pages: 372-379
  • NAID: 130004246704
  • Peer Reviewed
• [Journal Article] A genome wide association study identifies an associate on of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis (2008)
  • Author(s): Mushiroda T, Wattanapokayakit S, Takahashi A, Nukiwa T, et al
  • Journal Title: J Med Genet 45 Pages: 654-656
  • Peer Reviewed
• [Journal Article] (2008)
  • Author(s): 貫和敏博, 他(日本呼吸器学会びまん性肺疾患学術部会他)
  • Journal Title: 気管支肺胞洗浄「BAL(bronchoalveolar lavage)」法の手引き(克誠堂出版) Pages: 3-4
• [Journal Article] Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan. (2008)
  • Author(s): Inoue Y., et. al.
  • Journal Title: Am J Respir Crit Care Med. 177 Pages: 752-762
  • Peer Reviewed
• [Journal Article] Epidemiology of sarcoidosis in Japan. (2008)
  • Author(s): Morimoto T., et. al.
  • Journal Title: Eur Respir J. 31 Pages: 372-379
  • Peer Reviewed
• [Journal Article] Mutations in the SLC34A2 gene are associated with pulmonary alveolar microlithiasis (2007)
  • Author(s): Huqun, Izumi S, Miyazawa H, Ishii K, Uchiyama B, Ishida T, Tanaka S, Tazawa R, Fukuyama S, Tanaka T, Nagai Y, Yokote A, Takahashi H, Fukushima T, Kobayashi K, Chiba H, Nagata M, Sakamoto S, Nakata K, Takebayashi Y, Shimizu Y, Kaneko K, Shimizu M, Kanazawa M, Abe S, Inoue Y, Takenoshita S, Yoshimura K, Kudo K, Tachibana T, Nukiwa T, Hagiwara K.
  • Journal Title: Am J Respir Crit Care Med. 175(3) Pages: 263-268
  • Peer Reviewed
• [Journal Article] Mutations in the SLC34A2 gene are associated with pulmonary alveolar microlithiasis. (2007)
  • Author(s): Huqun, et. al.
  • Journal Title: Am J Respir Crit Care Med. 175 Pages: 263-268
  • Peer Reviewed
• [Presentation] Translational medicine in lung fibrosis (2010)
  • Author(s): Nukiwa T
  • Organizer: PIPKRA VIII
  • Place of Presentation: Jakarta
  • Year and Date: 2010-02-14
• [Presentation] 特発性間質性肺炎 (2009)
  • Author(s): 貫和敏博
  • Organizer: 第49回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-06-13
• [Presentation] Simultaneous Alterations of Gene Expressions in Different Cell Types of Alveolar Septa Induced by Transforming Growth Factor-beta 1 and Recovered by Cyclosporin A (2009)
  • Author(s): Hirota N, Ohta H, Tamai T, Nukiwa T, Ebina M
  • Organizer: American Thoracic Society International conference
  • Place of Presentation: San Diego
  • Year and Date: 2009-05-17
• [Presentation] 特発性肺線維症 (2008)
  • Author(s): 貫和敏博
  • Organizer: 第48回日本呼吸器学会学術講演会 Respiratory Year in Review5
  • Place of Presentation: 東京
  • Year and Date: 2008-06-16
• [Presentation] OX40L-OX40 Interactions contribute to NKT Activation in a Mouse Model of Allergic Airway disease (2008)
  • Author(s): Zaini J, Andarini S, Kikuchi T, Nukiwa T
  • Organizer: American Thoracic Society International conference
  • Place of Presentation: Toronto
  • Year and Date: 2008-05-16
• [Presentation] A Phase III, Double-Blind, Placebo-Controlled clinical Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis in Japan (2008)
  • Author(s): Ogura T, Ebina M, Taniguchi H, Azuma A, Suga M, Taguchi Y, Nakata K, Sato A, Nukiwa T, Kudoh S
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: Toronto
  • Year and Date: 2008-05-16
• [Presentation] Idiopathic Pulmonary Fibrosis and Acute Exacerbations Current Concept and Possible Interventions (2008)
  • Author(s): Nukiwa T
  • Organizer: Bangladesh Lung Foundation Pulmocon 2008
  • Place of Presentation: Bangladesh
  • Year and Date: 2008-02-17
• [Presentation] Idiopathic Pulmonary Fibrosis and acute Exacerbations current concept and possible inter ventions (2008)
  • Author(s): Nukiwa T
  • Organizer: Bangladesh Lung Foundation Pulmocon
  • Place of Presentation: Dhaka(Bangladesh)
  • Year and Date: 2008-02-17
• [Presentation] Accumulation of Activating Mutations in EGF Receptor Kinase among Patients with Lung Adenocarcinoma in Asia: Biological Implication and Clinical Aspects (2007)
  • Author(s): Toshihiro Nukiwa
  • Organizer: Asian Pacific Society of Respirology
  • Place of Presentation: Gold Coast Convention, Australia
  • Year and Date: 2007-12-02
• [Presentation] Exacerbation in interstitial lung disease : A clear picture? (2007)
  • Author(s): Nukiwa T
  • Organizer: European Respiratory Society Annual Meeting 2007
  • Place of Presentation: Stockholm
  • Year and Date: 2007-09-18
• [Book] 呼吸器疾患最新の治療 2010-2012. (貫和敏博、杉山幸比古、門田淳一編集) (2010)
  • Author(s): 貫和敏博, 他
  • Publisher: 南江堂
• [Book] The role of biomarkers in management of interstitial lung disease : implication of biomarkers derived from type II pneumocytes. Du Bois RM and Richeldi L Edt. The European Respiratory Monograph (2009)
  • Author(s): Nukiwa T
  • Publisher: European Respiratory Society
• [Book] 気管支肺胞洗浄法「BAL」の手引き. (日本呼吸器学会びまん性肺疾患学術部会、厚生労働省難治性疾患克服研究事業びまん性肺疾患調査研究班、編集 : 貫和敏博) (2008)
  • Author(s): 貫和敏博, 他
  • Publisher: 克誠堂出版
• [Book] 内科診断学第2版 (2008)
  • Author(s): 貫和敏博(共著、福井次矢、奈良信雄編集)
  • Publisher: 医学書院