A new strategy for treatment of lung fibrosis; Identification of a complementary peptide which inhibited PDGF/PDGFR signaling pathway

• Project/Area Number: 25461160
• 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: AZUMA Momoyo 徳島大学, 大学病院, 特任講師 (10403750)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ペプチド / 肺線維症 / PDGF / PDGFR / 抗線維化ペプチド

Outline of Final Research Achievements

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis. The molecular mechanisms involved in the progression of IPF are not fully understood. However, the platelet-derived growth factor (PDGF)/PDGF receptor pathway is thought to play a critical role in fibrogenesis of the lungs. In the present study, we investigated whether the targeted inhibition of PDGF signal by using a complementary peptide, has the potential to regulate pulmonary fibrosis. Complementary peptides inhibited the proliferation of lung fibroblasts in response to PDGF. Additionally, we showed that complementary peptides bind to the surface of lung fibroblasts using immunofluorescence staining. Transbronchial administration of complementary peptides ameliorated the pulmonary fibrosis induced by bleomycin in mice. These data suggest that it can become a promising target for therapeutic approaches to pulmonary fibrosis.

Research Products

• [Journal Article] Role of PDGF/PDGFR 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) Pages: 793-801
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ブレオマイシン肺線維症モデルにおけるFAKシグナル阻害薬の抗線維化効果 (2014)
  • Author(s): 木下勝弘, 青野純典, 竹﨑彰夫, 岡﨑弘泰, 吉嶋輝実, 岸昌美, 東桃代, 岸潤, 泉啓介, 西岡安彦.
  • Journal Title: 分子呼吸器病 Volume: 18(1) Pages: 154-157
  • Acknowledgement Compliant
• [Journal Article] Targeting platelet-derived growth factor as a therapeutic approach in pulmonary fibrosis. (2013)
  • Author(s): Nishioka Y, Azuma M, Kishi M, Aono Y.
  • Journal Title: J Med Invest. Volume: 60 Pages: 175-183
  • NAID: 130004822680
• [Presentation] 岸昌美, 青野純典, 東桃代, 木下勝弘, 佐藤正大, 吉嶋輝実, 竹﨑彰夫, 西岡安彦. PDGFレセプター-α, β阻害抗体のブレオマイシン誘発肺線維症モデルマウスにおける抗線維化効果 (2014)
  • Author(s): 岸昌美, 青野純典, 東桃代, 木下勝弘, 佐藤正大, 吉嶋輝実, 竹﨑彰夫, 西岡安彦
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪国際会場（大阪府大阪市）
  • Year and Date: 2014-04-26
• [Presentation] PDGFレセプター-α, β阻害抗体のブレオマイシン誘発肺線維症モデルマウスにおける抗線維化効果 (2014)
  • Author(s): 岸昌美, 青野純典, 東桃代, 木下勝弘, 佐藤正大, 吉嶋輝実, 竹﨑彰夫, 西岡安彦
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪国際会議場(大阪府）
• [Book] Pathogenesis of IPF. Is abnormal repair of epithelial damage involved in the basic pathogenesis of this disease? (2016)
  • Author(s): Yasuhiko Nishioka.
  • Total Pages: 259
  • Publisher: Springer Japan.
• [Book] IPFの病因論. (2015)
  • Author(s): 西岡安彦.
  • Total Pages: 103
  • Publisher: THE LUNG