Platelet-derived growth factor receptors expressed in response to injury of differentiated vascular smooth muscle in vitro: effects on Ca2+ and growth signals.
Vascular smooth muscle cells (VSMCs) in the intact vascular wall are differentiated for contraction, whereas the response to vascular injury involves transition towards a synthetic phenotype, with increased tendency for proliferation. Platelet-derived growth factor (PDGF) is thought to be important for this process. We investigated expression and functional coupling of PDGF receptors (PDGFRs) alpha and beta in rat tail arterial rings kept in organ culture, in order to capture early events in the phenotypic transition. In freshly dissected rings no PDGFR immunoreactivity was found in medial VSMCs, whereas PDGFR alpha was detected in nerve fibres. After organ culture for 1-4 days PDGFR alpha and beta as well as phospholipase Cgamma2 (PLCgamma2), known to couple to PDGFR, were expressed in VSMCs within 100 microm of the cut ends. Calponin, a marker for the contractile phenotype, was decreased near the injured area, suggesting that cells were in transition towards synthetic phenotype. In these cells, which showed functional Ca2+-release from the sarcoplasmic reticulum, PDGF-AB (100 ng x mL(-1)) had no effect on [Ca2+]i, whereas cultured VSMCs obtained from explants of rat tail arterial rings responded to PDGF-AB with an increase in [Ca2+]i. However, PDGFR within the cultured rings coupled to growth signalling pathways, as PDGF-AB caused a tyrphostin AG1295-sensitive activation of extracellular signal-regulated kinases 1 and 2 and of [3H]-thymidine incorporation. Thus, early expression of PDGFR in VSMC adjacent to sites of vascular injury coincides with signs of dedifferentiation. These receptors couple to growth signalling, but do not activate intracellular Ca2+ release.
Lindqvist
A
A
Department of Physiological Sciences, Lund University, Lund, Sweden.
Nilsson
B O
BO
Ekblad
E
E
Hellstrand
P
P
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000032:analysis; D002454:Cell Differentiation; D004247:DNA / Q000096:biosynthesis; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008840:Microfilament Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000293:injuries* / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D009924:Organ Culture Techniques; D051966:Phospholipase C gamma; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis / Q000096:biosynthesis*; D010738:Type C Phospholipases / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D000096985:Calponins
D002118:Calcium; D002135:Calcium-Binding Proteins; D004247:DNA; D007527:Isoenzymes; D008840:Microfilament Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009638:Norepinephrine; D051966:Phospholipase C gamma; D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D010738:Type C Phospholipases; D014662:Vasoconstrictor Agents; D000096985:Calponins; C095477:platelet-derived growth factor AB