Differential expression of platelet-derived growth factor-alpha receptor by Thy-1(-) and Thy-1(+) lung fibroblasts.
Fibroblasts are heterogeneous with respect to surface markers, morphology, and participation in fibrotic responses. This study was undertaken to determine whether Thy-1(-) and Thy-1(+) rat lung fibroblasts, which have distinct and relevant phenotypes, differ in their proliferative responses to platelet-derived growth factor (PDGF) isoforms. Homogeneous populations of Thy-1(-) and Thy-1(+) fibroblasts were found to proliferate equally in the presence of PDGF-BB, but PDGF-AA-mediated proliferation occurred only in Thy-1(-) cells. This differential activity correlated with significantly higher expression of PDGF-alpha receptor in Thy-1(-) fibroblasts as shown by immunoblotting, immunofluorescence, and Northern blotting. There was a rapid increase in c-myc mRNA in Thy-1(-) but not in Thy-1(+) fibroblasts on stimulation with PDGF-AA and PDGF-BB. The PDGF-alpha receptor, which mediates signaling by all PDGF isoforms, has been implicated in numerous clinical and experimental forms of fibrosis and regulates lung morphogenesis. Differential expression of the PDGF-alpha receptor supports distinct roles for Thy-1(-) and Thy-1(+) fibroblast populations in developmental and fibrotic processes in the lung.
Hagood
J S
JS
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. jhagood@peds.uab.edu
Miller
P J
PJ
Lasky
J A
JA
Tousson
A
A
Guo
B
B
Fuller
G M
GM
McIntosh
J C
JC
D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D007425:Intracellular Membranes / Q000502:physiology; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D018800:Thy-1 Antigens / Q000032:analysis*
D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D018800:Thy-1 Antigens; C075278:platelet-derived growth factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor