Platelet-derived Growth Factor Receptor In Vanadium

Environmental Health Sciences

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Abstract

Studies were conducted to investigate whether platelet derived growth factor receptor-alpha (PDGF-Ra) is upregulated following intratracheal instillation of vanadium pentoxide (V2O5) in rats. Rats were instilled with 2 mg/kg V2O5 and expression of PDGF-Ra and -Rb measured at various times post-treatment. PDGF-Ra mRNA expression was induced 24 hours post-instillation. PDGF-Rb mRNA was expressed constituitively and did not increase. Immunohistochemical analysis localized PDGF-Ra primarily in mesenchymal cells located within fibrotic lesions. Upregulation of PDGF-Ra preceded mesenchymal cell hyperplasia (3-7 days) and collagen deposition by day 15. In an attempt to correlate these effects of V2O5 with functional changes, pulmonary function was evaluated in treated rats. Rats were instilled with a fibrogenic dose of V2O5 and pulmonary function measured 1, 2, and 4 weeks after dosing. Lungs were collected from subgroups of treated animals at these time points for histological evaluation. The pulmonary function parameters of treated rats were not significantly changed by V2O5 although histological evidence of pulmonary fibrosis was present. Additional studies are planned to investigate further the time course for V2O5 pulmonary toxicity in COX-1 and ?2 knock out mice. Previous experiments demonstrated a significant induction of pulmonary fibrosis in V2O5-treated COX-2 mice.