bFGF and PDGF-BB have a synergistic effect on the proliferation, migration and VEGF release of endothelial progenitor cells.
We have investigated the synergistic effects of bFGF (basic fibroblast growth factor) and PDGF-BB (platelet-derived growth factor-BB) on the proliferation, migration and VEGF (vascular endothelial growth factor) release of EPCs (endothelial progenitor cells). The proliferation of EPCs was assayed by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium]. EPCs migration was detected using the Transwell system. Real-time PCR was used to assess the transcription of PDGFRβ mRNA. PLC-γ (phospholipase C gamma) expression and VEGF release were analysed by Western blot and ELISA. bFGF and PDGF-BB could, respectively, or synergistically, promote the proliferation and migration of EPCs, and these effects of bFGF and PDGF-BB were implemented by enhancing PDGFRβ mRNA, PLC-γ and VEGF expression, while inhibitor of PDGF receptor kinase (AG1296) and the selective PLC inhibitor (U73122) could block these effects of bFGF and PDGF-BB. In the meantime, we proved that the amplification by bFGF and PDGF-BB-stimulated PDGFRβ mRNA, PLC-γ and VEGF expression was abrogated by anti-bFGF antibody, AG1296 and U73122. These results strongly suggest that the proliferation and migration of EPCs may depend on bFGF and/or PDGF-BB by PDGFRβ/PLC-γ signalling pathway, and bFGF and/or PDGF-BB stimulate VEGF release at a point downstream from PDGFRβ/PLC-γ in EPCs.
Department of Pathology, China Medical University Affiliated Shengjing Hospital, Shenyang, People's Republic of China.
Guo
G
Sufen
Yang
Y
Xianghong
Cheng
C
Yongxia
Pan
P
Qian
D000818:Animals; D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051966:Phospholipase C gamma / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D051966:Phospholipase C gamma