Elucidaring WNT/beta-catenin in acute exacerbation of idiopathic pulmonary fibrosis after lung cancer surgery

• Project/Area Number: 26860621
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: ISHIMOTO Hiroshi 産業医科大学, 医学部, 講師 (00457558)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 特発性肺線維症 / 急性増悪 / WNT/β-catenin signaling / wnt10A / WNT10A / 肺癌 / 術後

Outline of Final Research Achievements

We evaluated the expression of WNT10A and TGF-β in bleomycin (BLM)-treated mice and the interactions between TGF-β or BLM and WNT10A in vitro. Additionally, we investigated IPF patients who underwent video-assisted thoracoscopic surgery to determine whether the WNT10A expression is related to the survival.
Increased WNT10A and TGF-β expressions were noted in the BLM-treated mice. Real-time PCR and luciferase reporter assays demonstrated the levels of WNT10A and collagen in the fibroblasts cells to increase after TGF-β administration. A Kaplan-Meier survival analysis demonstrated a tendency toward a poor survival among the IPF patients with a WNT10A-positive expression compared to those with a negative expression. An overexpression of WNT10A was found to be significantly predictive of an acute exacerbation of IPF (AE-IPF).
WNT10A plays an important role in the pathogenesis of IPF via TGF-β activation and it may also be a sensitive predictor for the onset of an AE-IPF.

Research Products

• [Journal Article] Profibrotic role of WNT10A via TGF-β signaling in idiopathic pulmonary fibrosis. (2016)
  • Author(s): Oda K, Yatera K, Izumi H, Ishimoto H, Yamada S, Nakao H, Hanaka T, Ogoshi T, Noguchi S, Mukae H.
  • Journal Title: Respiratory Research Volume: 17 Issue: 1 Pages: 39-39
  • DOI: 10.1186/s12931-016-0357-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Autopsy analyses in acute exacerbation of idiopathic pulmonary fibrosis. (2014)
  • Author(s): Oda K, Ishimoto H, Yamada S, Kushima H, Ishii H, Imanaga T, Harada T, Ishimatsu Y, Matsumoto N, Naito K, Yatera K, Nakazato M, Kadota J, Watanabe K, Kohno S, Mukae H.
  • Journal Title: Respiratory Research Volume: １５ Issue: 1 Pages: 109-109
  • DOI: 10.1186/s12931-014-0109-y
  • NAID: 120006986405
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Case of immunoglobulin G4 (IgG4)-related disease diagnosed by transbronchial lung biopsy and endobronchial ultrasound-guided transbronchial needle aspiration. (2014)
  • Author(s): Ishimoto H, Yatera K, Shimabukuro I, Matsuki Y, Hanaka T, Oda K, Kawanami T, Mukae H.
  • Journal Title: J UOEH. Volume: 36
  • NAID: 110009878653
  • Peer Reviewed / Open Access
• [Presentation] The clinical and radiological features of acute lung injury in surgically treated patients with lung cancer complicating interstitial pneumonia; possible link to combined pulmonary fibrosis and emphysema (2014)
  • Author(s): Hiroshi Ishimoto, Kazuhiro Yatera, Keishi Oda, Toshinori Kawanami, Hidetaka Uramoto, Fumitaka Tanaka, Hiroshi Mukae
  • Organizer: American Thoracic Society International Conference 2014
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2014-05-16 – 2014-05-21