title: Expression of WNT5A in Idiopathic Pulmonary Fibrosis and Its Control by TGF-β and WNT7B in Human Lung Fibroblasts.
abstract: The wingless (Wnt) family of signaling ligands contributes significantly to lung development and is highly expressed in patients with usual interstitial pneumonia (UIP). We sought to define the cellular distribution of Wnt5A in the lung tissue of patients with idiopathic pulmonary fibrosis (IPF) and the signaling ligands that control its expression in human lung fibroblasts and IPF myofibroblasts. Tissue sections from 40 patients diagnosed with IPF or UIP were probed for the immunolocalization of Wnt5A. Further, isolated lung fibroblasts from normal or IPF human lungs, adenovirally transduced for the overexpression or silencing of Wnt7B or treated with TGF-β1 or its inhibitor, were analyzed for Wnt5A protein expression. Wnt5A was expressed in IPF lungs by airway and alveolar epithelium, smooth muscle cells, endothelium, and myofibroblasts of fibroblastic foci and throughout the interstitium. Forced overexpression of Wnt7B with or without TGF-β1 treatment significantly increased Wnt5A protein expression in normal human smooth muscle cells and fibroblasts but not in IPF myofibroblasts where Wnt5A was already highly expressed. The results demonstrate a wide distribution of Wnt5A expression in cells of the IPF lung and reveal that it is significantly increased by Wnt7B and TGF-β1, which, in combination, could represent key signaling pathways that modulate the pathogenesis of IPF.
authors.affiliation: Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, and Center for Human Health and the Environment, College of Sciences, North Carolina State University, Raleigh, North Carolina (DRN, WSS, KH, AZ, KMT, EC, PLS).
authors.forename: Donna R
authors.initials: DR
authors.lastname: Newman
authors.affiliation: Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, and Center for Human Health and the Environment, College of Sciences, North Carolina State University, Raleigh, North Carolina (DRN, WSS, KH, AZ, KMT, EC, PLS).
authors.forename: W Shane
authors.initials: WS
authors.lastname: Sills
authors.affiliation: Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, and Center for Human Health and the Environment, College of Sciences, North Carolina State University, Raleigh, North Carolina (DRN, WSS, KH, AZ, KMT, EC, PLS).
authors.forename: Katherine
authors.initials: K
authors.lastname: Hanrahan
authors.affiliation: Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, and Center for Human Health and the Environment, College of Sciences, North Carolina State University, Raleigh, North Carolina (DRN, WSS, KH, AZ, KMT, EC, PLS).
authors.forename: Amanda
authors.initials: A
authors.lastname: Ziegler
authors.affiliation: Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, and Center for Human Health and the Environment, College of Sciences, North Carolina State University, Raleigh, North Carolina (DRN, WSS, KH, AZ, KMT, EC, PLS).
authors.forename: Kathleen McGinnis
authors.initials: KM
authors.lastname: Tidd
authors.affiliation: Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, and Center for Human Health and the Environment, College of Sciences, North Carolina State University, Raleigh, North Carolina (DRN, WSS, KH, AZ, KMT, EC, PLS).
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cook
authors.affiliation: Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, and Center for Human Health and the Environment, College of Sciences, North Carolina State University, Raleigh, North Carolina (DRN, WSS, KH, AZ, KMT, EC, PLS).
authors.forename: Philip L
authors.initials: PL
authors.lastname: Sannes
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D051153:Wnt Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D000071818:Wnt-5a Protein
chemical_list: D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; C085389:WNT5A protein, human; C490675:WNT7B protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein
keywords: IPF; Wnt5A; Wnt7B; alveolar epithelium; myofibroblast; smooth muscle cells