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2017 ; 15
(4
): 1981-1988
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English Wikipedia
Slit2 suppresses endothelial cell proliferation and migration by inhibiting the
VEGF-Notch signaling pathway
#MMPMID28260032
Li GJ
; Yang Y
; Yang GK
; Wan J
; Cui DL
; Ma ZH
; Du LJ
; Zhang GM
Mol Med Rep
2017[Apr]; 15
(4
): 1981-1988
PMID28260032
show ga
Slit homolog 2 (Slit2) is distributed in various tissues and participates in
numerous cellular processes; however, the role of Slit2 in the regulation of
angiogenesis remains controversial, since it has previously been reported to
exert proangiogenic and antiangiogenic activities. The present study aimed to
investigate the effects of Slit2 on vascular endothelial cell proliferation and
migration in vitro, and to reveal the possible underlying signaling pathway.
Aortic endothelial cells were isolated from Sprague Dawley rats and cultured.
Cell proliferation assay, cell migration assay, immunocytochemistry and small
interfering RNA transfection were subsequently performed. The results
demonstrated that exogenous Slit2 administration markedly suppressed
TNF???induced endothelial cell proliferation and migration in vitro. In addition,
TNF?? application upregulated the protein expression levels of vascular
endothelial growth factor (VEGF) and Notch in RAECs, whereas Slit2 administration
downregulated VEGF and Notch expression in RAECs cultured in TNF?? conditioned
medium. Further studies indicated that knockdown of VEGF suppressed the effects
of TNF?? on the induction of RAEC proliferation and migration. VEGF
knockdown?induced inhibition of RAEC proliferation and migration in TNF??
conditioned medium was also achieved without Slit2 administration. Furthermore,
VEGF knockdown markedly decreased Notch1 and Notch2 expression. These results
indicated that Slit2 suppresses TNF???induced vascular endothelial cell
proliferation and migration in vitro by inhibiting the VEGF?Notch signaling
pathway. Therefore, Slit2 may inhibit the proliferation and migration of
endothelial cells during vascular development.
|*Cell Movement
[MESH]
|*Cell Proliferation
[MESH]
|*Signal Transduction
[MESH]
|Animals
[MESH]
|Aorta/cytology
[MESH]
|Cells, Cultured
[MESH]
|Endothelial Cells/*cytology/metabolism
[MESH]
|Intercellular Signaling Peptides and Proteins/*metabolism
[MESH]