Comparative study of transforming growth factor-β signalling and regulatory molecules in human and canine idiopathic pulmonary fibrosis.

Activation of transforming growth factor (TGF)-β is a key event in the progression of fibrosis in human lung tissue. Idiopathic pulmonary fibrosis (IPF) in West Highland white terriers (WHWTs) shares histopathological features of human usual interstitial pneumonia (UIP), the histopathological counterpart of IPF and non-specific interstitial pneumonia (NSIP). The aim of the present immunohistochemical study was to investigate TGF-β signalling activity and its known extracellular matrix (ECM) regulatory proteins, latent TGF-β binding protein (LTBP)-1 and fibrillin-2, in lung tissue of WHWTs with IPF and healthy WHWTs and to compare these with findings in human UIP and NSIP. P-Smad2 immunoreactivity, indicating TGF-β signalling activity, was increased in WHWTs with IPF relative to healthy WHWTs and expression was localized predominantly in the altered alveolar epithelium, as seen in both UIP and NSIP. Increased peribronchial and perivascular LTBP-1 immunoreactivity was seen in WHWTs with IPF compared with controls, possibly indicating the importance of the small airways in the canine disease. Alveolar LTPB-1 immunolabelling in diseased WHWTs was seen mainly in the altered alveolar epithelium, resembling more closely the labelling in UIP than in NSIP. Alveolar interstitial fibrillin-2 immunoreactivity, which is up-regulated in the lungs of people with UIP, was also detected in the lungs of WHWTs with IPF and people with NSIP. However, no significant difference was seen between WHWTs with IPF and control WHWTs. The results suggest that increased TGF-β signalling and expression of the ECM regulatory proteins LTBP-1 and fibrillin-2 are part of the molecular pathophysiology of canine IPF.