Journal
MICROVASCULAR RESEARCH
Volume 71, Issue 3, Pages 152-162Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mvr.2006.01.001
Keywords
endostatin; endothelial morphology; protein phosphatase 2A; restin; ERK1/2-kinase
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Endostatin, the proteolytic fragment of collagen XVIII, is known to be a potent inhibitor of angiogenesis. However, to date, only limited knowledge exists with regard to the effects of endostatin on vessel morphology and the underlying signaling pathway. The aim of the present work was therefore to determine the impact of endostatin and its collagen XV analogue restin on vessel development during wound healing and embryonic angio- and vasculogenesis. Time lapse experiments and electron microscopy demonstrate similar morphological changes evoked by endostatin and the ERK1/2-kinase inhibitor PD98059. Furthermore, we show that ERK1/2 phosphorylation, a crucial signaling event in vascular morphogenesis, is regulated by endostatin via the protein phosphatase 2A PP2A. These findings provide new insight into a key signaling pathway of vascular remodeling evoked by a matrix-derived factor. (c) 2006 Elsevier Inc. All rights reserved.
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