Anti-fibrotic function of Surfactant Protein-D in bleomycin induced lung fibrosis

• Project/Area Number: 24591167
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: The University of Tokushima
• Principal Investigator: AONO Yoshinori 徳島大学, ヘルスバイオサイエンス研究部, 非常勤講師 (50398004)
• Co-Investigator(Kenkyū-buntansha): GOTO Hisatsugu 徳島大学, 大学院ヘルスバイオサイエンス研究部, 講師 (00437641)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: SP-D / 増殖因子 / 肺線維症 / fibrocyte / マクロファージ / サーファクタント

Outline of Final Research Achievements

Serum SP-D concentration is an important biomarker in patients with idiopathic pulmonary fibrosis, but its role in lung fibrosis is unknown. We examined the role of SP-D in bleomycin (BLM) induced pulmonary fibrosis model using SP-D conditional mice. BLM-treated SP-D off mice had increased lung fibrois compared to SP-D on mice. SP-D deficiency also increased macrophage and fibrocyte-dominant cell infiltration and the expression of growth factors (TGF-beta, PDGF) from the cells in the lung of BLM treated mice. These data suggest that alveolar SP-D regulates numbers of macrophages and fibrocytes in the lungs, growth factor expression, and fibrotic lung remodeling in response to BLM injury

Research Products

• [Journal Article] IMD-4690, a Novel Specific Inhibitor for Plasminogen Activator Inhibitor-1, Reduces Allergic Airway Remodeling in a Mouse Model of Chronic Asthma via Regulating Angiogenesis and Remodeling-Related Mediators. (2015)
  • Author(s): Tezuka T, Ogawa H, Azuma M, Goto H, Uehara H, Aono Y, Hanibuchi M, Yamaguchi Y, Fujikawa T, Itai A, Nishioka Y
  • Journal Title: PLoS One Volume: 10(3) Issue: 3 Pages: e0121615-e0121615
  • DOI: 10.1371/journal.pone.0121615
  • Peer Reviewed
• [Journal Article] Surfactant protein D attenuates sub-epithelial fibrosis in allergic airways disease through TGF-β. (2014)
  • Author(s): Ogawa H, Ledford JG, Mukherjee S, Aono Y, Nishioka Y, Lee JJ, Izumi K, Hollingsworth JW.
  • Journal Title: Respir Res Volume: 15(1) Issue: 1 Pages: 143-143
  • DOI: 10.1186/s12931-014-0143-9
  • Peer Reviewed
• [Journal Article] Role of platelet-derived growth factor/platelet-derived growth factor receptor axis in the trafficking of circulating fibrocytes in pulmonary fibrosis. (2014)
  • Author(s): Aono Y, Kishi M, Yokota Y, Azuma M, Kinoshita K, Takezaki A, Sato S, Kawano H, Kishi J, Goto H, Uehara H, Izumi K, Nishioka Y
  • Journal Title: Am J Respir Cell Mol Biol. Volume: 51(6) Issue: 6 Pages: 793-801
  • DOI: 10.1165/rcmb.2013-0455oc
  • Peer Reviewed
• [Journal Article] Thymidine phosphorylase regulates the expression of CXCL10 in rheumatoid arthritis fibroblast-like synoviocytes (2014)
  • Author(s): Toyoda Y, Tabata S, Kishi J, Kuramoto T, Mitsuhashi A, Saijo A, Kawano H, Goto H, Aono Y, Hanibuchi M, Horikawa H, Nakajima T, Furukawa T, Sone S, Akiyama S, Nishioka Y
  • Journal Title: Arthritis & Rheumatology Volume: 66(3) Issue: 3 Pages: 560-568
  • DOI: 10.1002/art.38263
  • Peer Reviewed / Open Access
• [Journal Article] Antifibrotic Effects of Focal Adhesion Kinase Inhibitor in Bleomycin-induced Pulmonary Fibrosis in Mice (2013)
  • Author(s): Kinoshita K
  • Journal Title: Am J Respir Cell Mol Biol Volume: inpress
  • Peer Reviewed
• [Journal Article] Antifibrotic effects of CXCR4 antagonist in bleomycin-induced pulmonary fibrosis in mice (2013)
  • Author(s): Makino H
  • Journal Title: J Med Invest Volume: 60 Pages: 127-137
  • Peer Reviewed
• [Journal Article] Surfactant protein a suppresses lung cancer progression by regulating the polarization of tumor-associated macrophages. (2013)
  • Author(s): Mitsuhashi A, Yano S, et al.
  • Journal Title: Am J Pathol Volume: 182 Issue: 5 Pages: 1843-53
  • DOI: 10.1016/j.ajpath.2013.01.030
  • Peer Reviewed
• [Presentation] Fibrocyte Regulates Lung Fibroblast Activation via Producing Growth Factors (2013)
  • Author(s): Aono Y, Abe S, Kinoshita K, Kishi M, Nishioka Y
  • Organizer: 18th congress of the Asian Pacific Society of Respirology
  • Place of Presentation: The conference center, Pacifico Yokohama (Kanagawa)
• [Presentation] Different functions of PDGF receptor -α and-β in lung fibrosis (2012)
  • Author(s): Aono Y
  • Organizer: American Thoracic Society
  • Place of Presentation: Moscone Center (USA)
• [Presentation] Fibrocyte Regulates Lung Fibroblast Activation (2012)
  • Author(s): Abe S
  • Organizer: American Thoracic Society
  • Place of Presentation: Moscone Center (USA)