Abstract
Introduction: Wound remodelling in the pathogenesis of idiopathic pulmonary fibrosis (IPF) has produced conflicting results from previous cell culture and animal model studies.
Aim: The aim of this study was to examine wound remodelling mechanisms in usual interstitial pneumonia (UIP), with emphasis on the role of epithelial mesenchymal transition (EMT).
Methods: Immunohistochemistry was used to assess cellular expressions of markers of EMT in paraffin embedded lung tissue samples from 21 patients with IPF, with comparisons made to histologicaly-defined normal lung sections from 19 control subjects.
Results: Hyperplastic type II pneumocytes in all UIP cases expressed the adhesion molecule E-cadherin with no expression of N-cadherin or TWIST. Expression of TWIST was restricted to the fibroblasts/myofibroblasts. TGF-β protein was consistently expressed by type II pneumocytes of UIP samples, but to varying degrees within the fibroblastic foci. Collagen I and smooth muscle actin were expressed in the fibroblastic foci.
Conclusions: Myofibroblasts may form a contractile repair response to a micro-injury via secretion of extracellular matrix proteins, providing scaffolding for type II pneumocytes which then divide at the edge of the insult and migrate over the fibroblastic foci surface. TGF-β signalling pathways may lead to the continued accumulation of type I collagen in the foci. Alternatively, abnormal collagen I is produced which is resistant to matrix metalloproteinases inhibiting wound repair. We conclude that tissue remodelling in IPF is a complex processes warranting further investigations to fully elucidate the role of EMT in the pathogenesis of IPF.
- © 2011 ERS