Expression of WNT5A in Idiopathic Pulmonary Fibrosis and Its Control by TGF-β and WNT7B in Human Lung Fibroblasts
| Autor: | Katherine Hanrahan, W. Shane Sills, Elizabeth Cook, Amanda L. Ziegler, Donna R. Newman, Philip L. Sannes, Kathleen McGinnis Tidd |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Histology Myocytes Smooth Muscle Wnt-5a Protein Pathogenesis 03 medical and health sciences Idiopathic pulmonary fibrosis Usual interstitial pneumonia Transforming Growth Factor beta Proto-Oncogene Proteins Medicine Humans Gene Silencing Myofibroblasts Lung Cells Cultured business.industry Wnt signaling pathway Articles respiratory system Fibroblasts medicine.disease Idiopathic Pulmonary Fibrosis respiratory tract diseases Up-Regulation WNT5A body regions Wnt Proteins 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation embryonic structures sense organs Anatomy business Myofibroblast Transforming growth factor |
| Zdroj: | The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 64(2) |
| ISSN: | 1551-5044 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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