Upregulation of the PDGF-alpha receptor precedes asbestos-induced lung fibrosis in rats.
Platelet-derived growth factor-AA (PDGF-AA) and its matching alpha receptor (PDGF-R alpha) 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 alpha 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 alpha peptide expression 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 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 alpha-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.
Lasky
J A
JA
Department of Medicine, Tulane University Medical Center, New Orleans, Louisiana 70112, USA.
Tonthat
B
B
Liu
J Y
JY
Friedman
M
M
Brody
A R
AR
D000818:Animals; D001195:Asbestosis / Q000150:complications / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism*; D008297:Male; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D015854:Up-Regulation
D012333:RNA, Messenger; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor