Endostatin influences endothelial morphology via the activated ERK1/2-kinase endothelial morphology and signal transduction

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.