Contribution of epithelial-to-mesenchymal transition to phenotypic changes in idiopathic interstitial pneumonias

Idiopathic interstitial pneumonias cause fibrosis in which lungs become scarred due to the increase number of myofibroblasts and excess extracellular matrix deposition. Structural alterations in the interstitium of lung parenchyma are associated with significant mortality and morbidity. Epithelial-to-mesenchymal transition (EMT) is a process whereby epithelial cells undergo transition to a mesenchymal phenotype. This process has been shown to contribute to idiopathic pulmonary fibrosis (IPF) but contribution to nonspecific interstitial pneumonitis (NSIP) is unknown We investigated whether EMT was present in patients with IPF (n = 10) or NSIP (n = 6), using immunohistochemistry and confocal microscopy. All patients had surgical lung biopsies. Normal lung tissue obtained from lobectomies was also evaluated.We performed immunostaining for E-cadherin, p63, CK14 and the signature EMT markers N-cadherin and Vimentin. In addition we performed immunofluorecent staining for N-cadherin, p63 and Vimentin. We show that p63 positive basal cells are present in the overlying epithelium adjacent to fibrotic foci in IPF. This basal epithelium has acquired increased mesenchymal markers (N-cadherin,Vimentin) and increased CK14 while retaining E-cadherin expression. The underlying fibrotic foci showed both E- and N-cadherin positive cells.Samples from patients with NSIP had much less responses to CK14, Vimentin, p63 and N-cadherin than patients with IPF. This was related to fewer numbers of fibroblastic foci. Cells positive for p63 were found in alveoli and terminal bronchioles in NSIP but not normal controls. Results suggest that EMT is differently involved in pathogenesis of IPF than NSIP.