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Erythropoietin and Vascular Endothelial Growth Factor induce activation of Matrix Metalloproteinase‐2 via a common pathway
Author(s) -
Ispanovic Eric,
Haas Tara L
Publication year - 2008
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.22.1_supplement.925.10
Subject(s) - angiogenesis , erythropoietin , vascular endothelial growth factor , matrix metalloproteinase , erythropoietin receptor , microbiology and biotechnology , growth factor , pi3k/akt/mtor pathway , chemistry , endothelial stem cell , cancer research , basement membrane , medicine , endocrinology , receptor , signal transduction , biology , vegf receptors , biochemistry , in vitro
Angiogenesis is the formation of new capillaries from pre‐existing ones. Proteolysis of the basement membrane and interstitial matrix is mediated by the matrix metalloproteinases (MMPs) and is critical to the angiogenic process. Recent research has found that a number of cell types outside of the bone marrow, including endothelial cells, express the erythropoietin (EPO) receptor and respond to EPO. The angiogenic potential of EPO has been shown to be on par with that of vascular endothelial growth factor (VEGF). Little is known about how EPO induces angiogenesis. EPO treatment (2.5 nM, 2 hrs) induced cortical actin polymerization and increased the amount of MT1‐MMP on the cell surface similarly to the response seen with VEGF treatment (25 ng/mL, 2 hrs). The increase in cell surface localization correlated with an increase in MMP‐2 activation in response to both EPO and VEGF treatment. Both EPO and VEGF activated the PI3K/P‐AKT pathway and required PI3K activity for MMP‐2 activation. Together, these data provide new insight into the mechanisms by which EPO may induce angiogenesis, thus improving our understanding of the physiological roles of EPO. Funded by NSERC.