Changes in pulmonary endothelial cell and fibroblast properties during bleomycin-induced pulmonary fibrosis

• Project/Area Number: 17K09609
• 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: Hamamatsu University School of Medicine
• Principal Investigator: Inui Naoki 浜松医科大学, 医学部, 教授 (80402254)
• Co-Investigator(Kenkyū-buntansha): 須田 隆文 浜松医科大学, 医学部, 教授 (30291397)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 間質性肺炎 / 肺線維症 / 線維化 / 肺線維化 / ブレオマイシン

Outline of Final Research Achievements

Pulmonary fibrosis is a progressive and lethal disease characterized by damage to the lung parenchyma with excess extracellular matrix deposition. Levels of von Willebrand factor, plasminogen activator inhibitor-1 and matrix metalloproteinase-12 were elevated in lung endothelial cells isolated from bleomycin-treated mice, which indicated that intratracheal bleomycin administration induced endothelium injury. Expression of fibrogenic mediators was elevated in the cells from bleomycin-treated. When endothelial cells were treated with TGF-β, α-smooth muscle actin expression and collagen production were increased.

Academic Significance and Societal Importance of the Research Achievements

肺線維化は上皮細胞の障害によって生じると考えられている。今回の研究によって、ブレオマイシンによる肺障害では、内皮細胞もダメージを受けており、この障害された肺血管内皮細胞は、内皮機能の低下していること、TGF-βなど種々の刺激への感受性が高く、血管内皮細胞が肺の線維化が進行していく一因となっている可能性が示唆された。

Research Products

• [Journal Article] CD248 and integrin alpha-8 are candidate markers for differentiating lung fibroblast subtypes (2020)
  • Author(s): Matsushima Sayomi、Aoshima Yoichiro、Akamatsu Taisuke、Enomoto Yasunori、Meguro Shiori、Kosugi Isao、Kawasaki Hideya、Fujisawa Tomoyuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Funai Kazuhito、Suda Takafumi、Iwashita Toshihide
  • Journal Title: BMC Pulmonary Medicine Volume: 20 Issue: 1 Pages: 1-1
  • DOI: 10.1186/s12890-020-1054-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical significance of serum S100 calcium-binding protein A4 in idiopathic pulmonary fibrosis. (2019)
  • Author(s): Akiyama N, Hozumi H, Isayama T, Okada J, Sugiura K, Yasui H, Suzuki Y, Kono M, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Inui N, Nakamura Y, Suda T.
  • Journal Title: Respirology Volume: 0 Issue: 7 Pages: 0-0
  • DOI: 10.1111/resp.13707
  • NAID: 120007097006
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis. (2018)
  • Author(s): Kato S, Inui N*, Hakamata A, Suzuki Y, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T.
  • Journal Title: Respir Res. Volume: 19 Issue: 1 Pages: 127-127
  • DOI: 10.1186/s12931-018-0831-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Clinical Utility of Serum S100 Calcium Binding Protein A4 in Idiopathic Pulmonary Fibrosis (2019)
  • Author(s): Akiyama N, Hozumi H, Yasui H, Kono M, Suzuki Y, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Inui N, Nakamura Y, Suda T
  • Organizer: American Thoracic Society
  • Int'l Joint Research
• [Presentation] ブレオマイシン誘発性肺線維症モデルマウスにおける肺血管内皮細胞の変化 (2019)
  • Author(s): 加藤 慎平、乾 直輝、袴田 晃央、鈴木 勇三、榎本 紀之、藤澤 朋幸、中村 祐太郎、渡邊 裕司、須田 隆文
  • Organizer: 日本呼吸器学会学術講演会