VEGF-A stimulates podosome-mediated collagen-IV proteolysis in microvascular endothelial cells - PubMed (original) (raw)

. 2016 Jul 1;129(13):2586-98.

doi: 10.1242/jcs.186585. Epub 2016 May 26.

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VEGF-A stimulates podosome-mediated collagen-IV proteolysis in microvascular endothelial cells

Thomas Daubon et al. J Cell Sci. 2016.

Abstract

Podosomes are dynamic cell-matrix contact structures that combine several key abilities, including adhesion, matrix degradation and mechanosensing. These actin-based cytoskeletal structures have been mostly studied in monocytic cells, but much less is known about those formed in other lineages. In this study, we characterise podosomes in capillary-derived microvascular endothelial cells. We identify two types of podosomes: constitutive podosomes that form in the absence of specific stimulation and induced podosomes that arise in response to the angiogenic factor VEGF-A. Constitutive and VEGF-A-induced podosomes share similar components but exhibit marked differences in terms of gelatinolytic activity. We also show that the extracellular matrix proteins laminin and collagen-IV are key determinants of the VEGF-A response, but neither collagen-I nor fibronectin are conducive for podosome induction. Moreover, only collagen-IV elicits the formation of proteolytically active podosomes through a mechanism involving increased Src phosphorylation, p190RhoGAP-B (also known as ARHGAP5) relocalisation and MT1-MMP (also known as MMP14) cell surface exposure at podosome sites. We hypothesise that by promoting podosome formation, VEGF-A enables endothelial cells to overcome the basement membrane barrier to allow sprouting outwards from the existing vasculature.

Keywords: Basement membrane; Collagen-IV; Endothelial cells; Podosomes; VEGF-A.

© 2016. Published by The Company of Biologists Ltd.

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