Role of canstatin in early fibrotic lesions of idiopathic interstitial pneumonias and migration of lung fibroblasts

Early fibrotic lesions are thought to be one of the initial findings of lung fibrogenesis in idiopathic interstitial pneumonias, but little is known about their properties. Canstatin is an endogenous angiogenesis inhibitor derived from the C-terminal globular non-collagenous domain of the α2 chain of type IV collagen, and type IV collagen is deposited in early fibrotic lesions without neovascularization in usual interstitial pneumonia (UIP). We used immunohistochemical methods to study expression of canstatin in lung specimens from patients with UIP or organizing pneumonia (OP). We analyzed the expression and function of canstatin in cultured lung fibroblasts by Western blotting and a Boyden chamber migration assay. We found expression of canstatin in early fibrotic lesions of UIP but not OP. Lung fibroblasts showed enhanced expression of canstatin after being stimulated with transforming growth factor-b1. Recombinant canstatin inhibited migration of not only endothelial cells but also lung fibroblasts. These results suggest that fibroblasts in early fibrotic lesions of UIP, which express canstatin, have less ability to migrate than fibroblasts in OP lesions, which do not express canstatin. Thus, canstatin in early fibrotic lesions of UIP contributes to persistent fibrogenesis and is likely involved in its refractory nature, including migration of intralesional fibroblasts.