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Endothelial signaling of matrix‐bound and diffusible VEGF
Author(s) -
Logsdon Elizabeth A.,
Woo Laura,
Mac Gabhann Feilim
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.682.11
Subject(s) - fibronectin , microbiology and biotechnology , vascular endothelial growth factor , angiogenesis , integrin , extracellular matrix , signal transduction , chemistry , matrix (chemical analysis) , kinase insert domain receptor , vascular endothelial growth factor a , receptor , growth factor , cell adhesion molecule , biology , cancer research , vegf receptors , biochemistry , chromatography
Angiogenesis is a complex morphogenesis process coordinating endothelial cell (EC) signaling through matrix/integrin pathways and growth factor/receptor pathways, including the vascular endothelial growth factor (VEGF) family and their receptors. VEGF is presented to ECs in two modes – freely diffusing or bound to the extracellular matrix (ECM). While most studies have focused on diffusible VEGF, matrix‐bound VEGF also induces receptor activation resulting in unique signaling. Using a combination of experimental and computational methods, we examine how fibronectin, a component of the ECM known to bind VEGF, influences EC responses. Receptor activation, trafficking, and intracellular signaling are predicted to be highly altered for matrix‐binding VEGF. We independently control VEGF presentation mode and matrix‐integrin signals in vitro. Results indicate that diffusible VEGF is a stronger signal for VEGF receptor and adhesion molecule expression. Human microvascular ECs exhibit starkly different morphology based on the ratio of matrix‐bound to diffusible VEGF, with increased cell‐cell contact for diffusible VEGF. Thus, VEGF presentation mode controls EC behavior. Supported by NIH R00HL093219