Endorepellin evokes autophagy in endothelial cells.

摘要: Endorepellin, the C-terminal fragment of heparan sulfate proteoglycan perlecan, possesses angiostatic activity via dual receptor antagonism, through concurrent binding to α2β1 integrin and vascular endothelial growth factor 2 (VEGFR2). Here, we discovered that soluble endorepellin induced autophagy in cells by modulating expression Beclin 1, LC3, p62, three established autophagic markers. Moreover, evoked imprinted tumor suppressor gene Peg3 its co-localization with 1 LC3 autophagosomes, suggesting a major role for this cell autophagy. Mechanistically, down-regulating VEGFR2 two LG1/2 domains, whereas LG3 domain, portion responsible integrin, was ineffective. Endorepellin also transcriptional BECN1 promoter cells, VEGFR2-specific tyrosine kinase inhibitor, SU5416, blocked effect. Finally, found correlation between endorepellin-evoked inhibition capillary morphogenesis enhanced Thus, have identified new endogenous inducing VEGFR2-dependent but integrin-independent pathway. This novel mechanism specifically targets could represent promising strategy potentiate effect perhaps other matrix proteins.