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Am J Physiol Lung Cell Mol Physiol 274: L72-L80, 1998;
1040-0605/98 $5.00
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Vol. 274, Issue 1, L72-L80, January 1998

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

James C. Bonner1, Pamela M. Lindroos1, Annette B. Rice1, Cindy R. Moomaw2, and Daniel L. Morgan3

Laboratories of 1 Pulmonary Pathobiology, 2 Experimental Pathology, and 3 Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

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

lung fibrosis; vanadium pentoxide; platelet-derived growth factor-receptor system; interleukin-1; transforming growth factor-beta 1


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