Notch1 mediates visfatin-induced FGF-2 up-regulation and endothelial angiogenesis

Title
Notch1 mediates visfatin-induced FGF-2 up-regulation and endothelial angiogenesis
Author(s)
김정애배윤희[배윤희]박현주[박현주]김수련[김수련]김지영[김지영]강유라위희준[위희준]카케야마 료이치로[카케야마 료이치로]정진섭[정진섭]배문경[배문경]배수경[배수경]
Keywords
FIBROBLAST GROWTH FACTOR-2; COLONY-ENHANCING FACTOR; INHIBITS TUMOR-GROWTH; GAMMA-SECRETASE; ACTIVATION; EXPRESSION; CELLS; DLL4; MACROPHAGES; PATHWAY
Issue Date
201102
Publisher
OXFORD UNIV PRESS
Citation
CARDIOVASCULAR RESEARCH, v.89, no.2, pp.436 - 445
Abstract
Aims Our aims were to determine the role of Notch1 in mediating visfatin-induced angiogenesis and to explore potential target genes involved. Methods and results Inhibition of Notch signalling attenuated visfatin-induced angiogenesis in vitro, ex vivo, and in vivo. Visfatin increased gamma-secretase activity, Notch1 cleavage and activation, and Hes1 gene induction. Visfatin also stimulated fibroblast growth factor-2 (FGF-2) gene expression in a Notch1-dependent manner. Enforced expression of active Notch1 intracellular domain increased FGF-2 protein levels and stimulated endothelial tube formation, whereas blocking Notch1 signalling or knockdown of Notch1 by small interfering RNA suppressed visfatin- induced FGF-2 up-regulation and angiogenesis. Reporter analysis of FGF-2 promoter revealed the presence of CSL (CBF-1, suppressor of hairless, LAG-1)-binding site, and chromatin immunoprecipitation analysis demonstrated the binding of Notch1-CSL complex to this site in response to visfatin. Conclusion Our data provide the first example of Notch1-dependent endothelial FGF-2 induction by visfatin and of Notch1 activation in visfatin-stimulated endothelial angiogenesis, suggesting that the signalling axis of visfatin/Notch1/angiogenic factors like FGF-2 might be a valuable target for pathological angiogenesis.
URI
http://hdl.handle.net/YU.REPOSITORY/25681http://dx.doi.org/10.1093/cvr/cvq276
ISSN
0008-6363
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약학대학 > 약학부 > Articles
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