Expression of vascular endothelial growth factor receptors in smooth muscle cells.
Vascular Endothelial Growth Factor (VEGF) has been typically considered to be an endothelial-specific growth factor. However, it was recently demonstrated that VEGF can interact with non endothelial cells. In this study, we tested whether vascular smooth muscles cells (VSMCs) can express VEGF receptors, such as flk-1, flt-1, and neuropilin (NP)-1, and respond to VEGF in vitro. In cultured VSMCs, flk-1 and flt-1 expression was inversely related to cell density. The expression of flk-1 was down-regulated with increasing passage numbers. However, NP-1 levels were not affected by cell density or passage numbers. Flk-1, Flt-1, and NP-1 protein levels were confirmed by Western Blotting. Although the functional mature form of Flk-1 protein is expressed at low levels in VSMCs, phosphorylation of Flk-1 following VEGF(165) stimulation was still observed. SMCs migrated significantly in response to VEGF(165) and VEGF-E, whereas Placenta Growth Factor (PlGF) induced migration only at higher concentrations. Since VEGF-E is a specific activator of flk-1 while PlGF specifically activates only flt-1, SMC migration induced by VEGF(165) is likely to be mediated primarily through the flk-1 receptor. VSMCs did not significantly proliferate in response to VEGF(165), PlGF, and VEGF-E. In conclusion, our studies demonstrate the presence of VEGF receptors on VSMCs that are functional. These studies also indicate that in vivo, VEGF may play a role in modulating the response of VSMCs.
Ishida
A
A
Department of Molecular Biology, The Hope Heart Institute, Seattle, Washington 98122, USA.
Murray
J
J
Saito
Y
Y
Kanthou
C
C
Benzakour
O
O
Shibuya
M
M
Wijelath
E S
ES
D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D004285:Dogs; D016228:Endothelial Growth Factors / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D008222:Lymphokines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D039942:Neuropilin-1; D010766:Phosphorylation; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors; D014764:Viral Proteins / Q000494:pharmacology
D016228:Endothelial Growth Factors; D008222:Lymphokines; D009419:Nerve Tissue Proteins; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; C084758:VEGF-like protein, Orf virus; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014764:Viral Proteins; D000072483:Placenta Growth Factor; D039942:Neuropilin-1; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1