4.5 Article

Neuritin promotes angiogenesis through inhibition of DLL4/Notch signaling pathway

Journal

ACTA BIOCHIMICA ET BIOPHYSICA SINICA
Volume 53, Issue 6, Pages 663-672

Publisher

SCIENCE PRESS
DOI: 10.1093/abbs/gmab039

Keywords

neuritin; angiogenesis; Notch signaling pathway; delta-like ligand 4

Funding

  1. National Natural Science Foundation of China [NSFe81771173]
  2. Key Project of the Shihezi University [2015ZRKXYQ20]

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Neuritin plays a crucial role in angiogenesis and may affect angiogenesis by inhibiting the Notch signaling pathway. The expression of Neuritin is decreased in lung cancer vascular tissue but is correlated with increased vascular density. Overexpression of Neuritin can suppress the Notch signaling pathway and enhance the migration and tubular formation of HUVECs.
Neuritin is a member of the neurotrophic factor family, which plays an important role in the promotion and development of the nervous system. Neuritin is also involved in angiogenesis. Neuritin was recently found to be a negative regulatory factor of the Notch 1 signaling pathway. Notch signaling pathway is known as a regulatory pathway of angiogenesis. Thus, neuritin may play a role in angiogenesis through the Notch signaling pathway. In the present study, we investigated the expressions of neuritin and Notch signaling pathway factors in the pulmonary vascular tissue. The results showed that neuritin expression was increased in the paraneoplastic vascular tissue and decreased in the lung cancer vascular tissue. The neuritin expression was increased with the increase of vascular tissue density, and a negative correlation between neuritin expression and delta-like ligand 4 (DLL4) was identified in vascular tissues of lung cancer. Overexpression of neuritin in human umbilical vein endothelial cells (HUVECs) inhibited the expressions of Notch signaling pathway-associated factors, including DLL4, NICD, and Hes-1, and promoted the migration and tubular formation of HUVECs. In conclusion, our results indicated that neuritin is involved in angiogenesis and may play a role in angiogenesis through the Notch signaling pathway. This study provides a theoretical basis for clinical anti-angiogenesis therapy.

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