Efficacy of PAR-2 antagonists in lung fibrosis

• Project/Area Number: 23591159
• 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: Fukushima Medical University (2013-2014); Saitama Medical University (2011-2012)
• Principal Investigator: SUZUKI TOMOKO 福島県立医科大学, 公私立大学の部局等, 准教授 (10400342)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 肺線維症急性増悪 / 国際情報交流

Outline of Final Research Achievements

Pathogenetic mechanisms of idiopathic interstitial pneumonias (IIPs) remain unclear. Epithelial-to-mesenchymal transition (EMT) may play a key in the pathogenesis of fibrosis. Transforming growth factor (TGF)-beta is known to induce the transformation of fibroblasts to myofibroblasts and EMT of epithelium. Protease activated receptor (PAR)-2 has been recognized as a key molecule regulating inflammation and fibrosis. We hypothesized that PAR-2 activation induces TGF-beta and EMT.
Functional PAR-2 was expressed on lung epithelium. PAR-2 activation by trypsin or PAR-2AP induced TGF-beta. PAR-2 activation led to cleavage of E-cadherin and induction of vimentin expression. These phenomena were blocked by PAR-2 inhibiting peptide. PAR-2 activation induces TGF-beta and EMT of lung epithelium, processes that may contribute to lung fibrosis. PAR-2 may be a key molecule driving lung fibrosis and thus represent a novel therapeutic target.

Research Products

• [Presentation] 間質性肺炎におけるPAR-2の役割について (2014)
  • Author(s): 鈴木朋子
  • Organizer: 日本呼吸器学会
  • Place of Presentation: 東京
• [Presentation] PAR-2 agonists induce TGF-beta and EMT leading to lung fibrosis. (2013)
  • Author(s): Tomoko Suzuki
  • Organizer: European Respiratory Society
  • Place of Presentation: Barcelona, Spain
• [Presentation] PAR-2 agonists induce TGF-beta and EMT leading to lung fibrosis. (2013)
  • Author(s): Tomoko Suzuki
  • Organizer: European Respiratory Soceity
  • Place of Presentation: Barcelona, Spain