Effect of growth factor-fibronectin matrix interaction on rat type II cell adhesion and DNA synthesis

Type II cells attach, migrate, and proliferate on a provisional fibronectin-rich matrix during alveolar wall repair after lung injury. The combination of cell-substratum interactions via integrin receptors and exposure to local growth factors are likely to initiate the signals required for cell proliferation, differentiation, reepithelialization, and ultimate restoration of the alveolar wall structure. Accordingly, primary cultured type II cells have been shown to bind fibronectin, in part through the alpha5beta1 integrin, and to respond to growth factors that induce type II cell proliferation, such as fibroblast growth factor 1 (FGF-1). The purpose of this study was to determine whether or not FGF-1 modifies type II cell attachment to fibronectin, and if together they affect DNA synthesis. Attachment assays showed that FGF-1 treatment enhanced type II cell adhesion to fibronectin. This effect correlated with an increase in beta1 integrin cell surface expression, and with the formation of cytoskeletal stabilizing structures such as lamellipodial extensions and stress fibers. FGF-1 also induced an increase in thymidine incorporation into DNA. Together FGF-1 and fibronectin appear to promote adhesion, cytoskeletal organization, and increased DNA synthesis, and in this way influence cell-substratum interactions and signaling during alveolar repair.