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- Title
Profibrotic role of WNT10A via TGF-β signaling in idiopathic pulmonary fibrosis.
- Authors
Keishi Oda; Kazuhiro Yatera; Hiroto Izumi; Hiroshi Ishimoto; Sohsuke Yamada; Hiroyuki Nakao; Tetsuya Hanaka; Takaaki Ogoshi; Shingo Noguchi; Hiroshi Mukae; Oda, Keishi; Yatera, Kazuhiro; Izumi, Hiroto; Ishimoto, Hiroshi; Yamada, Sohsuke; Nakao, Hiroyuki; Hanaka, Tetsuya; Ogoshi, Takaaki; Noguchi, Shingo; Mukae, Hiroshi
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>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.
- Subjects
DISEASE exacerbation; IDIOPATHIC pulmonary fibrosis; TRANSFORMING growth factors; AUTOPSY; MONOCYTE chemotactic factor; ANIMAL experimentation; BLEOMYCIN; CELL culture; CELLULAR signal transduction; FIBROBLASTS; GLYCOPROTEINS; GROWTH factors; MICE; NERVE tissue proteins; SURVIVAL
- Publication
Respiratory Research, 2016, Vol 17, p1
- ISSN
1465-9921
- Publication type
journal article
- DOI
10.1186/s12931-016-0357-0