Proteomics

Dataset Information

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VEGF Study in Primary Human Endothelial Cells

ABSTRACT: The process of angiogenesis is under complex regulation in adult organisms, particularly as it often occurs in an inflammatory post-wound environment. As such, there are many impacting factors that will regulate the generation of new blood vessels which include not only pro-angiogenic growth factors such as vascular endothelial growth factor, but also angiostatic factors. During initial post-wound hemostasis, a large initial bolus of platelet factor 4 is released into localized areas of damage prior to progression of wound healing toward tissue homeostasis. Due to its early presence and high concentration, the angiostatic chemokine platelet factor 4, which can induce endothelial anoikis, can strongly affect angiogenesis. In our work, we explored signaling crosstalk interactions between vascular endothelial growth factor and platelet factor 4 using phosphotyrosine-enriched mass spectrometry methods on human dermal microvascular endothelial cells cultured under conditions facilitating migratory sprouting into collagen gel matrices. We developed new methods to enable mass spectrometry-based phosphorylation analysis of primary cells cultured on collagen gels, and quantified signaling pathways over the first 48 hours of treatment with vascular endothelial growth factor in the presence or absence of platelet factor 4. By observing early and late signaling dynamics in tandem with correlation network modeling, we found that platelet factor 4 has significant crosstalk with vascular endothelial growth factor by modulating cell migration and polarization pathways, centered around P38α MAPK, Src family kinases Fyn and Lyn, along with FAK. Interestingly, we found EphA2 correlational topology to strongly involve key migration-related signaling nodes after introduction of platelet factor 4, indicating an influence of the angiostatic factor on this ambiguous but generally angiogenic signal in this complex environment.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Nathan Tedford  

PROVIDER: PXD000462 | Pride | 2014-04-15

REPOSITORIES: Pride

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Publications

Vascular endothelial growth factor (VEGF) and platelet (PF-4) factor 4 inputs modulate human microvascular endothelial signaling in a three-dimensional matrix migration context.

Hang Ta-Chun TC   Tedford Nathan C NC   Reddy Raven J RJ   Rimchala Tharathorn T   Wells Alan A   White Forest M FM   Kamm Roger D RD   Lauffenburger Douglas A DA  

Molecular & cellular proteomics : MCP 20130909 12

The process of angiogenesis is under complex regulation in adult organisms, particularly as it often occurs in an inflammatory post-wound environment. As such, there are many impacting factors that will regulate the generation of new blood vessels which include not only pro-angiogenic growth factors such as vascular endothelial growth factor, but also angiostatic factors. During initial postwound hemostasis, a large initial bolus of platelet factor 4 is released into localized areas of damage be  ...[more]