UP-REGULATION OF THE PDGF-ALPHA RECEPTOR PRECEDES ASBESTOS-INDUCED LUNG FIBROSIS IN RATS

Platelet-derived growth factor-AA (PDGF-AA) and its matching alpha rec eptor (PDGF-R alpha) are upregulated in rat lung fibroblasts (RLFs) af ter exposure to chrysotile asbestos fibers in vitro, which results in asbestos-induced RLF proliferation. We now report our in vivo observat ions, which show an increase in the expression of PDGF-R alpha mRNA, b ut not PDGF-beta receptor mRNA, in asbestos-exposed rat lungs when com pared with RNA from air-exposed (sham) and iron-exposed lungs. Western analysis of membrane preparations confirmed the observations on mRNA expression by demonstrating an increase in PDGF-R alpha peptide expres sion in the asbestos-exposed rat lungs, compared with that in the air- exposed lungs. Immunohistochemistry for the PDGF-R alpha was performed on air- and asbestos-exposed rat lungs and revealed a clear increase in staining within interstitial and subepithelial compartments in the exposed animals. These observations, along with our previous report de monstrating an increase in the PDGF-AA isoform expression immediately after asbestos-exposure, suggest a scenario in which a potent lung mes enchymal cell mitogen, PDGF-AA, and its alpha-receptor are upregulated prior to the development of a fibroproliferative lung lesion, and thu s may play a central role in the pathogenesis of asbestos-induced lung fibrosis.