The role of Src-homology 2 domain containing tyrosine phosphatase 2 in growth factor dependent endothelial signalling and angiogenesis

摘要: Endothelial cell survival is indispensable to maintain endothelial integrity and initiate new vessel formation. We investigated the role of SHP-2 in proliferation, sprouting human microvascular- umbilical vein cells (HMEC, HUVEC) using antisense oligonucleotides (AS-ODN) a pharmacological inhibitor (PtpI IV). Knock-down decreased bFGF PDGF dependent proliferation (p<0.01; n=12) as compared nonsense oligonucleotide (NS-ODN) treatment. Cell cycle analysis by flow cytometric propidium iodide staining (p<0.01, n=6) subsequent Annexin V (p<0.05, n=9) revealed significantly higher number apoptotic following AS-ODN transfection. Furthermore, inhibition impaired formation capillary like structures well Matrigel embedded mouse aortic rings ex vivo. Finally, this was associated with phosphorylation PI3-Kinase, Akt ERK1/2. Our results indicate that promotes possibly growth factor PI3-K MAP kinase activation, necessary for These observations suggest be key enzyme control angiogenesis.