title: Differential regulation of the genes encoding platelet-derived growth factor receptor and its ligand in rat lung during microvascular and alveolar wall remodeling in hyperoxia.
abstract: The growth factors that operate while the lung remodels in hyperoxia are not known. At the lung periphery, high oxygen levels cause cell hypertrophy and hyperplasia, and this results in a thickening of the alveolar-capillary membrane and the walls of its associated microvessels. The present study examines gene expression of platelet-derived growth factor (PDGF) receptor and its ligand in this region of the lung of rats breathing 87% oxygen and compares this with the levels of expression in normal lung. In similar peripheral lung tissue, the proliferative response of specific cell populations has been assessed by [3H]thymidine incorporation and autoradiography. Normal lung expresses PDGF alpha-receptor subunit transcripts of 6.5 and 4.7 kb and PDGF beta-receptor transcripts of 5.5 and 4.5 kb. PDGF A-chain transcripts of 2.9, 2.3, and 1.7 kb are also expressed, each being at 10-fold higher levels than the single 3.5-kb transcript detected for PDGF B-chain. Within hours of breathing high concentrations of oxygen, mRNA levels change rapidly for the PDGF receptor subunits. These levels return to normal after 1 day and then decline over the next 28 days of exposure. PDGF A-chain mRNA increases 12 to 18 h after exposure, but then returns to normal levels. It is the PDGF B-chain mRNA that responds most to hyperoxia by increasing 10-fold on day 3. This increase immediately precedes the proliferative response on day 4 of microvascular adventitial fibroblasts, precursor smooth muscle cells, and epithelial cells but not smooth muscle cells, which do not proliferate until day 28.
authors.affiliation: Department of Anesthesia, Massachusetts General Hospital, Charlestown 02129.
authors.forename: P P
authors.initials: PP
authors.lastname: Powell
authors.forename: C C
authors.initials: CC
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Jones
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002196:Capillaries / Q000378:metabolism; D005786:Gene Expression Regulation; D008024:Ligands; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor
chemical_list: D008024:Ligands; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor; D010100:Oxygen