Human vascular smooth muscle cells have at least two distinct PDGF receptors and can secrete PDGF-AA
- F. Hoffmann-La Roche Ltd., Basel (Switzerland)
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.
- OSTI ID:
- 5045189
- Journal Information:
- Journal of Cardiovascular Pharmacology; (USA), Journal Name: Journal of Cardiovascular Pharmacology; (USA); ISSN 0160-2446; ISSN JCPCD
- Country of Publication:
- United States
- Language:
- English
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550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
AZINES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BLOOD VESSELS
BODY
BODY FLUIDS
CARDIOVASCULAR SYSTEM
CELL CULTURES
CONNECTIVE TISSUE CELLS
CULTURE MEDIA
DAYS LIVING RADIOISOTOPES
DISEASES
DNA REPLICATION
ELECTRON CAPTURE RADIOISOTOPES
FIBROBLASTS
FUNCTIONS
GROWTH FACTORS
HETEROCYCLIC COMPOUNDS
IN VITRO
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MAN
MATERIALS
MEMBRANE PROTEINS
MICE
MITOGENS
MUSCLES
NUCLEI
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
PRIMATES
PROTEINS
PYRIMIDINES
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RIBOSIDES
RODENTS
SOMATIC CELLS
THYMIDINE
TRACER TECHNIQUES
VASCULAR DISEASES
VEINS
VERTEBRATES