May 9, 2009

Perlecan regulates developmental angiogenesis by modulating the VEGF-VEGFR2 axis

Matrix Biology : Journal of the International Society for Matrix Biology
Jason J ZoellerR V Iozzo

Abstract

Using the zebrafish, we previously identified a central function for perlecan during angiogenic blood vessel development. Here, we explored the nature of perlecan function during developmental angiogenesis. A close examination of individual endothelial cell behavior revealed that perlecan is required for proper endothelial cell migration and proliferation. Because these events are largely mediated by VEGF-VEGFR2 signaling, we investigated the relationship between perlecan and the VEGF pathway. We discovered that perlecan knockdown caused an abnormal increase and redistribution of total VEGF-A protein suggesting that perlecan is required for the appropriate localization of VEGF-A. Importantly, we linked perlecan function to the VEGF pathway by efficiently rescuing the perlecan morphant phenotype by microinjecting VEGF-A(165) protein or mRNA. Combining the strategic localization of perlecan throughout the vascular basement membrane along with its growth factor-binding ability, we hypothesized a major role for perlecan during the establishment of the VEGF gradient which provides the instructive cues to endothelial cells during angiogenesis. In support of this hypothesis we demonstrated that human perlecan bound in a heparan sulfat...Continue Reading

Mentioned in this Paper

Vertebrates
Embryo
Establishment and Maintenance of Localization
GRN gene
Prostatic Neoplasms
Biochemical Pathway
HS6ST1 gene
Tissue Membrane
Immunohistochemistry
Heparin

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