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10.3892/mmr.2017.6240

http://scihub22266oqcxt.onion/10.3892/mmr.2017.6240
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C5364956!5364956 !28260032
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suck abstract from ncbi


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pmid28260032
      Mol+Med+Rep 2017 ; 15 (4 ): 1981-1988
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  • 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]
  • |Nerve Tissue Proteins/*metabolism [MESH]
  • |Rats, Sprague-Dawley [MESH]
  • |Receptors, Notch/genetics/*metabolism [MESH]
  • |Slit Homolog 2 Protein [MESH]
  • |Tumor Necrosis Factor-alpha/metabolism [MESH]
  • |Up-Regulation [MESH]


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