Profibrotic role of WNT10A via TGF-β signaling in idiopathic pulmonary fibrosis

• Published in: Respiratory research Vol. 17; no. 39; p. 39
• Main Authors: Oda, Keishi, Yatera, Kazuhiro, Izumi, Hiroto, Ishimoto, Hiroshi, Yamada, Sohsuke, Nakao, Hiroyuki, Hanaka, Tetsuya, Ogoshi, Takaaki, Noguchi, Shingo, Mukae, Hiroshi
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12.04.2016; BioMed Central
• Subjects: Analysis; Animals; Bleomycin; Care and treatment; Cells, Cultured; Complications and side effects; Development and progression; Fibroblasts - metabolism; Fibroblasts - pathology; Histology, Pathological; Idiopathic Pulmonary Fibrosis - chemically induced; Idiopathic Pulmonary Fibrosis - metabolism; Idiopathic Pulmonary Fibrosis - pathology; Influence; Male; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins - metabolism; Pulmonary fibrosis; Survival Rate; Transforming Growth Factor beta - metabolism; Transforming growth factors; Wnt Proteins - metabolism; Wnt Signaling Pathway; Japan; Diffuse alveolar damage; WNT/β-catenin pathway; Acute exacerbation; Autopsy; Fibroblast; Idiopathic pulmonary fibrosis
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-016-0357-0

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. 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. 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). 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.