Human vascular smooth muscle cells have at least two distinct PDGF receptors and can secrete PDGF-AA.
Platelet-derived growth factor (PDGF), a potent mitogen and chemoattractant for smooth muscle cells and fibroblasts in culture, is believed to play an important role in the formation of proliferative lesions of arterio-sclerosis. PDGF appears as three different dimeric isoforms: AA, AB, and BB. These were recently found to bind to two different receptors, the A/B receptor (which binds all three isoforms) and the B receptor (which binds only PDGF-BB). To find out whether these receptors exhibit functional differences, we have monitored the binding and mitogenic activities of PDGF-AA and -BB in human umbilical vein smooth muscle cells (HSMCs), human dermal fibroblasts (HFs), and Swiss mouse 3T3 cells. With each cell type, there was a good correlation between the maximal levels of DNA synthesis achieved by these isoforms and the numbers of the appropriate receptor present on the cell surface: HMSCs, which have at least 32,000 B receptors but only 8,000 A/B receptors, responded well to PDGF-BB but responded poorly to PDGF-AA; whereas Swiss 3T3 cells, which have about equal numbers of B and A/B receptors (70,000 and 90,000, respectively), responded equally well to both isoforms. PDGF-AB was a more efficacious mitogen of HSMCs and HFs than was PDGF-AA and inhibited [125I]-PDGF-BB binding to HSMCs more effectively than PDGF-AA. This indicates that there may exist a third PDGF receptor type to which PDGF-BB and -AB but not PDGF-AA can bind.(ABSTRACT TRUNCATED AT 250 WORDS)
Hosang
M
M
Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Rouge
M
M
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007536:Isomerism; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000097:blood*; D017479:Receptors, Platelet-Derived Growth Factor; D013936:Thymidine / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism
D003470:Culture Media; D007457:Iodine Radioisotopes; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor; D013936:Thymidine