Induction of PDGF receptor-α 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-α (PDGF-Rα) in vitro enhances PDGF-induced mitogenesis and chemotaxis. Thus we investigated whether the PDGF-Rα is induced in vivo during pulmonary fibrogenesis using a vanadium pentoxide (V2O5) model of lung injury. PDGF-Rα mRNA expression was induced 24 h postinstillation. PDGF-Rβ mRNA was constitutively expressed and did not increase. Western blotting showed upregulation of PDGF-Rα protein by 48 h, and immunohistochemical analysis localized PDGF-Rα primarily in mesenchymal cells residing within fibrotic lesions. Upregulation of PDGF-Rα in vivo preceded mesenchymal cell hyperplasia (3–7 days) and collagen deposition by day 15. Supernatants from alveolar macrophages treated with V2O5in vitro released upregulatory activity for PDGF-Rα on cultured lung myofibroblasts, and this activity was blocked by the interleukin-1-receptor antagonist. These data suggest that interleukin-1β-mediated induction of PDGF-Rα in vivo is important to lung myofibroblast hyperplasia during fibrogenesis.