Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and lethal process of unknown etiology. The sub-pleural localization of fibrosis is a hallmark of early IPF but no link between the pleura and IPF has been established yet. We developed an experimental model of pleural fibrosis induced by adenovirus-mediated gene transfer of transforming growth factor (TGF)-beta1 to mesothelial cells and observed collagen accumulation within the pleura but also in the sub-pleural parenchyma. This sub-pleural fibrosis was associated, in vivo, with a mesothelial--to--myofibroblast transformation (mesothelio-fibroblastoid transformation), a process similar to the epithelial-mesenchymal transition. This phenotypic modification was also observed in vitro in mesothelial cells treated with recombinant TGF-beta1. These results suggest that mesothelial cells may have a central role not only in pleural fibrosis but also in the onset and progression of IPF.
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