| Autor: |
Rackow AR; Lung Biology and Disease Program, University of Rochester Medical Center Rochester, Rochester, New York.; Department of Environmental Medicine, University of Rochester Medical Center Rochester, Rochester, New York., Judge JL; Cook MyoSite, Inc., Pittsburgh, Pennsylvania., Woeller CF; Department of Environmental Medicine, University of Rochester Medical Center Rochester, Rochester, New York.; Department of Ophthalmology, University of Rochester Medical Center, Rochester, New York., Sime PJ; Division of Pulmonary Disease and Critical Care Medicine, Virginia Commonwealth University, Richmond, Virginia., Kottmann RM; Lung Biology and Disease Program, University of Rochester Medical Center Rochester, Rochester, New York.; Department of Environmental Medicine, University of Rochester Medical Center Rochester, Rochester, New York.; Division of Pulmonary Disease and Critical Care Medicine, University of Rochester Medical Center, Rochester, New York. |
| Abstrakt: |
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease. The pathogenesis of IPF is not completely understood. However, numerous genes are associated with the development and progression of pulmonary fibrosis, indicating there is a significant genetic component to the pathogenesis of IPF. Epigenetic influences on the development of human disease, including pulmonary fibrosis, remain to be fully elucidated. In this paper, we identify miR-338-3p as a microRNA severely downregulated in the lungs of patients with pulmonary fibrosis and in experimental models of pulmonary fibrosis. Treatment of primary human lung fibroblasts with miR-338-3p inhibits myofibroblast differentiation and matrix protein production. Published and proposed targets of miR-338-3p such as TGFβ receptor 1, MEK/ERK 1/2, Cdk4, and Cyclin D are also not responsible for the regulation of pulmonary fibroblast behavior by miR-338-3p. miR-338-3p inhibits myofibroblast differentiation by preventing TGFβ-mediated downregulation of phosphatase and tensin homolog (PTEN), a known antifibrotic mediator. |
