Platelet-Derived Growth Factor Blocks the Cell-Cycle Transition from the G0 to G1 Phase in Subcultured Angiogenic Endothelial Cells in Rat Thoracic Aorta
Ikuko Kimura, Hiroshi Tsuneki, Motonori Okabe and Masaru Ogasawara
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-01, Japan
Abstract: 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.
Keywords: Platelet-derived growth factor, Endothelial cell, Competence, Angiogenesis, Flow cytometry