title: Profibrotic role of WNT10A via TGF-β signaling in idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  WNT/β-catenin signaling plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF); however, the role of WNT10A via transforming growth factor (TGF)-β signaling remains unclear.
  
  
  METHODS
  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.
  
  
  RESULTS
  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. Conversely, WNT10A siRNA treatment inhibited the synthesis of collagen in the transfected fibroblasts cells. 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 (Hazard ratio 5.351, 95 % CI 1.703-16.82; p = 0.0041). An overexpression of WNT10A was found to be significantly predictive of an acute exacerbation of IPF (AE-IPF) (Odds ratio 13.69, 95 % CI 1.728-108.5; p = 0.013).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Oda
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan. yatera@med.uoeh-u.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yatera
authors.affiliation: Department of Occupational Pneumology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishimoto
authors.affiliation: Department of Pathology and Cell Biology, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.|Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
authors.forename: Sohsuke
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Miyazaki Prefectural Nursing University, 3-5-1 Manabino, Miyazaki City, Miyazaki, 880-0929, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakao
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hanaka
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ogoshi
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Noguchi
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan.|Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
mesh_terms: D000818:Animals; D001761:Bleomycin; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D054990:Idiopathic Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D009419:Nerve Tissue Proteins; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; C484143:Wnt10a protein, mouse; D001761:Bleomycin
keywords: Acute exacerbation; Autopsy; Diffuse alveolar damage; Fibroblast; Idiopathic pulmonary fibrosis; WNT/β-catenin pathway