Am. J. Respir. Crit. Care Med., Volume 157, Number 5, May 1998, 1652-1657

Upregulation of the PDGF-alpha Receptor Precedes Asbestos-induced Lung Fibrosis in Rats

JOSEPH A. LASKY, BOIHOANG TONTHAT, JING-YAO LIU, MITCHELL FRIEDMAN, and ARNOLD R. BRODY

Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine and Department of Pathology and Environmental Health Sciences, Tulane University Medical Center, New Orleans, Louisiana

Platelet-derived growth factor-AA (PDGF-AA) and its matching alpha receptor (PDGF-R) are upregulated in rat lung fibroblasts (RLFs) after exposure to chrysotile asbestos fibers in vitro, which results in asbestos-induced RLF proliferation. We now report our in vivo observations, which show an increase in the expression of PDGF-R mRNA, but not PDGF-beta receptor mRNA, in asbestos-exposed rat lungs when compared 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 peptide expression in the asbestos-exposed rat lungs, compared with that in the air-exposed lungs. Immunohistochemistry for the PDGF-R 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 demonstrating an increase in the PDGF-AA isoform expression immediately after asbestos-exposure, suggest a scenario in which a potent lung mesenchymal cell mitogen, PDGF-AA, and its -receptor are upregulated prior to the development of a fibroproliferative lung lesion, and thus may play a central role in the pathogenesis of asbestos-induced lung fibrosis.

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