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J Cell Sci. 2016 Jul 1;129(13):2586-98. doi: 10.1242/jcs.186585. Epub 2016 May 26.

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

Author information

1
Université de Bordeaux, 33 000 Bordeaux, France.
2
Université de Bordeaux, 33 000 Bordeaux, France INSERM U1045, 33 000 Bordeaux, France.
3
Université de Bordeaux, 33 000 Bordeaux, France INSERM U1045, 33 000 Bordeaux, France elisabeth.genot@inserm.fr.

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

PMID:
27231093
DOI:
10.1242/jcs.186585
[Indexed for MEDLINE]
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