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.
Schmidt
Annette
A
Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Germany.
Wenzel
Daniela
D
Thorey
Irmgard
I
Sasaki
Takako
T
Hescheler
Jürgen
J
Timpl
Rupert
R
Addicks
Klaus
K
Werner
Sabine
S
Fleischmann
Bernd K
BK
Bloch
Wilhelm
W
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D043169:Endostatins / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C076744:cytoplasmic linker protein 170; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3