Premium
Differential effects of various VEGF isoforms on endothelial cells and Tenon fibroblasts
Author(s) -
VAN BERGEN T,
VANDEWALLE E,
VAN DE VEIRE S,
MOONS L,
STALMANS I
Publication year - 2011
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2011.3134.x
Subject(s) - vascular endothelial growth factor , mapk/erk pathway , angiogenesis , vascular endothelial growth factor a , gene isoform , growth factor , signal transduction , microbiology and biotechnology , chemistry , cancer research , biology , medicine , vegf receptors , biochemistry , receptor , gene
Purpose We have previously shown that VEGF plays an important role in scar formation after glaucoma surgery. To clarify the differential effects elicited by VEGF isoforms, we compared the biological responses and signaling pathways activated by the various isoforms on endothelial cells and Tenon fibroblasts in vitro. Methods VEGF‐R2 and neuropilin‐1 (NRP‐1) expression was analyzed on endothelial cells (HUVEC) and Tenon fibroblasts (TF) by RT‐PCR. The effect of different VEGF isoforms (VEGF189, VEGF165 and VEGF121) on HUVEC and TF proliferation was determined by WST‐1 assay. The extracellular signal‐regulated kinase (ERK) pathway was evaluated by TransAM c‐Myc assay. Results HUVEC showed a higher expression of VEGF‐R2 and NRP‐1 mRNA as compared to TF. VEGF189 only significantly increased the growth of TF, whereas VEGF165 only increased HUVEC proliferation. VEGF165 strongly binds VEGF‐R2 and NRP‐1. As such, the combined reduced expression of VEGF‐R2 and NRP‐1 on TF explained why VEGF165 was more potent in inducing proliferation of HUVEC as compared to TF. VEGF121 exerted significant proliferative effects on both cell types by binding VEGF‐R2. However, similar concentrations of VEGF121 stimulated HUVEC more than TF, due to the lower expression of VEGF‐R2 on TF. All these stimulating effects on proliferation were associated with an activation of the ERK pathway. Conclusion Our data indicate that VEGF165 and VEGF121 predominantly affect blood vessel growth, whereas VEGF189 may be more important in fibrosis. Selective inhibition of VEGF165 (pegaptanib) may therefore be less effective to reduce ocular scar formation than non‐selective VEGF‐inhibition (bevacizumab), presumably due to retained action of VEGF121 and VEGF189.