Platelet-derived growth factor blocks the cell-cycle transition from the G0 to G1 phase in subcultured angiogenic endothelial cells in rat thoracic aorta.
Platelet-derived growth factor (PDGF)-BB induces tube formation by the differentiating (tube-forming) endothelial cells (EC) of rat thoracic aorta, although PDGF-BB does not affect the proliferative EC (increasing the cell numbers) at the progression phase. These changes in the responses to PDGF-BB were due to the phenotype-dependent expression of PDGF beta-receptor (PDGFR-beta) on EC because PDGFR-beta-like immunoreactivity was observed in the angiogenic EC forming a tube-like structure in 35-day culture with 10% fetal bovine serum, but not in the proliferative EC in 5-day culture. To elucidate the functional role of PDGFR-beta in the alteration of EC phenotype, the influence of PDGF-BB on the cell cycle of EC was investigated by flow cytometry. This analysis demonstrates that PDGF-BB blocks the transition from the G0 to G1 phase in the 35-day cultured EC, although no effect was observed on any phases of the cell cycle in 5-day culture. We conclude that 1) PDGFR-beta is expressed in mature angiogenic EC of rat aorta, and 2) PDGF-BB may contribute to promotion of the EC differentiation with tubular morphogenesis by inhibiting cell growth.
Kimura
I
I
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Tsuneki
H
H
Okabe
M
M
Ogasawara
M
M
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000077214:Becaplermin; D015153:Blotting, Western; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017208:Rats, Wistar; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*
D000927:Anticonvulsants; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor