Slit2 suppresses endothelial cell proliferation and migration by inhibiting the VEGF-Notch signaling pathway

Li,Guo‑Jian; Yang,Yong; Yang,Guo‑Kai; Wan,Jia; Cui,Dao‑Lei; Ma,Zhen‑Huan; Du,Ling‑Juan; Zhang,Gui‑Min

doi:10.3892/mmr.2017.6240

Slit2 suppresses endothelial cell proliferation and migration by inhibiting the VEGF-Notch signaling pathway

Authors:
- Guo‑Jian Li
- Yong Yang
- Guo‑Kai Yang
- Jia Wan
- Dao‑Lei Cui
- Zhen‑Huan Ma
- Ling‑Juan Du
- Gui‑Min Zhang
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Affiliations: Department of Vascular Surgery, The Fourth Affiliated Hospital, Kunming Medical University, Kunming, Yunnan 650021, P.R. China, Department of Cardiovascular Surgery, The First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan 650032, P.R. China
Published online on: February 22, 2017 https://doi.org/10.3892/mmr.2017.6240
Pages: 1981-1988
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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‑α‑induced endothelial cell proliferation and migration in vitro. In addition, TNF‑α 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‑α conditioned medium. Further studies indicated that knockdown of VEGF suppressed the effects of TNF‑α on the induction of RAEC proliferation and migration. VEGF knockdown‑induced inhibition of RAEC proliferation and migration in TNF‑α conditioned medium was also achieved without Slit2 administration. Furthermore, VEGF knockdown markedly decreased Notch1 and Notch2 expression. These results indicated that Slit2 suppresses TNF‑α‑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.

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