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Expression of vascular endothelial growth factor receptors in smooth muscle cells
Author(s) -
Ishida Atsushi,
Murray Jacqueline,
Saito Yuji,
Kanthou Chryso,
Benzakour Omar,
Shibuya Masabumi,
Wijelath Errol S.
Publication year - 2001
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1121
Subject(s) - vascular endothelial growth factor , vascular smooth muscle , receptor , neuropilin 1 , biology , medicine , endocrinology , vascular endothelial growth factor b , microbiology and biotechnology , vascular endothelial growth factor a , vascular endothelial growth factor c , growth factor , cancer research , vegf receptors , biochemistry , smooth muscle
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. © 2001 Wiley‐Liss, Inc.