Basic fibroblast growth factor is essential to maintain endothelial progenitor cell phenotype in TR-BME2 cells.
Endothelial progenitor cells (EPC) can differentiate into both endothelial cells and contractile smooth muscle cells (SMC). Previously we reported that TR-BME2 cells, a model for EPC, developed contractile SMC-like characteristics in culture medium deprived of endothelial cell growth factors (ECGF). The aim of the present study was to clarify the effect of one of these factors, basic fibroblast growth factor (bFGF) on differentiation of EPC. First it was confirmed that bFGF receptor (FGFR-1) mRNA is expressed in TR-BME2 cultured in both ECGF-rich and ECGF-deprived medium. When TR-BME2 cells were cultured in ECGF-deprived medium, they differentiated into contractile SMC. Expression of an undifferentiated state marker, CD133, and proliferation of TR-BME2 were both reduced by ECGF deprivation, but these changes were diminished in the presence of bFGF. mRNA expression of smooth muscle α-actin (SMA) and smooth muscle protein 22 (SM22), which are contractile SMC markers, was induced by deprivation of ECGF and the induction was suppressed by bFGF. In vascular endothelial cell growth factor (VEGF)-induced tube formation assay, TR-BME2 cells formed tube structures in the presence of bFGF, but not in its absence. Our results indicate that bFGF is essential for the maintenance of EPC phenotype, serving to suppress differentiation to contractile SMC.
Division of Pharmaceutics, Faculty of Pharmacy, Keio University.
Yoshimichi
Y
Sai
Tomohiro
T
Nishimura
Mariko
M
Muta
Hisashi
H
Iizasa
Takashi
T
Miyata
Emi
E
Nakashima
D000199:Actins / Q000096:biosynthesis*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D003470:Culture Media / Q000494:pharmacology; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D008840:Microfilament Proteins / Q000096:biosynthesis*; D009124:Muscle Proteins / Q000096:biosynthesis*; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D010641:Phenotype; D051381:Rats; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D000199:Actins; D015415:Biomarkers; D003470:Culture Media; D008840:Microfilament Proteins; D009124:Muscle Proteins; D042461:Vascular Endothelial Growth Factor A; C051615:transgelin; D016222:Fibroblast Growth Factor 2; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1