Normal Human Lung Epithelial Cells Inhibit Transforming Growth Factor-β Induced Myofibroblast Differentiation via Prostaglandin E2
| Autor: | Richard P. Phipps, Thomas H. Thatcher, Amali P. Epa, Lindsay A. Wahl, Elizabeth Lyda, Stephen J. Pollock, Patricia J. Sime, R.M. Kottmann |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Pathology
medicine.medical_specialty Cellular differentiation Primary Cell Culture lcsh:Medicine Gene Expression Biology Dinoprostone Extracellular matrix Idiopathic pulmonary fibrosis Fibrosis Transforming Growth Factor beta Pulmonary fibrosis medicine Humans lcsh:Science Fibroblast Myofibroblasts Cell Proliferation Multidisciplinary lcsh:R Cell Differentiation Epithelial Cells Transforming growth factor beta respiratory system Fibroblasts medicine.disease Antibodies Neutralizing Actins Coculture Techniques respiratory tract diseases 3. Good health medicine.anatomical_structure Cancer research biology.protein lcsh:Q Myofibroblast Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 8, p e0135266 (2015) |
| ISSN: | 1932-6203 |
| Popis: | INTRODUCTION:Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with very few effective treatments. The key effector cells in fibrosis are believed to be fibroblasts, which differentiate to a contractile myofibroblast phenotype with enhanced capacity to proliferate and produce extracellular matrix. The role of the lung epithelium in fibrosis is unclear. While there is evidence that the epithelium is disrupted in IPF, it is not known whether this is a cause or a result of the fibroblast pathology. We hypothesized that healthy epithelial cells are required to maintain normal lung homeostasis and can inhibit the activation and differentiation of lung fibroblasts to the myofibroblast phenotype. To investigate this hypothesis, we employed a novel co-culture model with primary human lung epithelial cells and fibroblasts to investigate whether epithelial cells inhibit myofibroblast differentiation. MEASUREMENTS AND MAIN RESULTS:In the presence of transforming growth factor (TGF)-β, fibroblasts co-cultured with epithelial cells expressed significantly less α-smooth muscle actin and collagen and showed marked reduction in cell migration, collagen gel contraction, and cell proliferation compared to fibroblasts grown without epithelial cells. Epithelial cells from non-matching tissue origins were capable of inhibiting TGF-β induced myofibroblast differentiation in lung, keloid and Graves' orbital fibroblasts. TGF-β promoted production of prostaglandin (PG) E2 in lung epithelial cells, and a PGE2 neutralizing antibody blocked the protective effect of epithelial cell co-culture. CONCLUSIONS:We provide the first direct experimental evidence that lung epithelial cells inhibit TGF-β induced myofibroblast differentiation and pro-fibrotic phenotypes in fibroblasts. This effect is not restricted by tissue origin, and is mediated, at least in part, by PGE2. Our data support the hypothesis that the epithelium plays a crucial role in maintaining lung homeostasis, and that damaged and/ or dysfunctional epithelium contributes to the development of fibrosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|