Induction of PDGF receptor-alpha in rat myofibroblasts during pulmonary fibrogenesis in vivo

Abstract

Platelet-derived growth factor (PDGF) is a potent mitogen for mesenchymal cells. Induction of the PDGF receptor-alpha (PDGF-R alpha) in vitro enhances PDGF-induced mitogenesis and chemotaxis. Thus we investigated whether the PDGF-R alpha is induced in vivo during pulmonary fibrogenesis using a vanadium pentoxide (V2O5) model of lung injury. PDGF-R alpha mRNA expression was induced 24 h postinstillation. PDGF-R beta mRNA was constitutively expressed and did not increase. Western blotting showed upregulation of PDGF-R alpha protein by 48 h, and immunohistochemical analysis localized PDGF-R alpha primarily in mesenchymal cells residing within fibrotic lesions. Upregulation of PDGF-R alpha in vivo preceded mesenchymal cell hyperplasia (3-7 days) and collagen deposition by day 15. Supernatants from alveolar macrophages treated with V2O5 in vitro released upregulatory activity for PDGF-R alpha on cultured lung myofibroblasts, and this activity was blocked by the interleukin-1-receptor antagonist. These data suggest that interleukin-1 beta-mediated induction of PDGF-R alpha in vivo is important to lung myofibroblast hyperplasia during fibrogenesis.