Expression of WNT5A in Idiopathic Pulmonary Fibrosis and Its Control by TGF-β and WNT7B in Human Lung Fibroblasts

J Histochem Cytochem. 2016 Feb;64(2):99-111. doi: 10.1369/0022155415617988. Epub 2015 Nov 4.


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.

Keywords: IPF; Wnt5A; Wnt7B; alveolar epithelium; myofibroblast; smooth muscle cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Gene Expression Regulation
  • Gene Silencing
  • Humans
  • Idiopathic Pulmonary Fibrosis / genetics
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Idiopathic Pulmonary Fibrosis / pathology*
  • Lung / metabolism
  • Lung / pathology*
  • Myocytes, Smooth Muscle / metabolism
  • Myofibroblasts / metabolism
  • Myofibroblasts / pathology
  • Proto-Oncogene Proteins / analysis*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Transforming Growth Factor beta / analysis*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation
  • Wnt Proteins / analysis*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • Wnt-5a Protein


  • Proto-Oncogene Proteins
  • Transforming Growth Factor beta
  • WNT5A protein, human
  • WNT7B protein, human
  • Wnt Proteins
  • Wnt-5a Protein