Netrin‑4 promotes VE‑cadherin expression in endothelial cells through the NF‑&kappa;B signaling pathway

Zhang,Datong; Zhu,Zhiying; Wen,Keting; Zhang,Shijie; Liu,Ju

doi:10.3892/etm.2024.12640

Netrin‑4 promotes VE‑cadherin expression in endothelial cells through the NF‑κB signaling pathway

Authors:
- Datong Zhang
- Zhiying Zhu
- Keting Wen
- Shijie Zhang
- Ju Liu
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Affiliations: Department of Orthodontics, School of Dentistry, Shandong University, Jinan, Shandong 250100, P.R. China, Institute of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
Published online on: July 4, 2024 https://doi.org/10.3892/etm.2024.12640
Article Number: 351
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Netrin‑4 (NTN4), a secreted protein from the Netrin family, has been recognized for its role in vascular development, endothelial homeostasis and angiogenesis. Vascular endothelial (VE)‑cadherin is a specialized adhesion protein located at the intercellular junctions of endothelial cells (ECs), and regulates migration, proliferation and permeability. To date, the relationship between NTN4 and VE‑cadherin in ECs remains unclear. In the present study, human umbilical vein ECs (HUVECs) were transfected with NTN4 overexpression plasmid, resulting in NTN4 overexpression. Reverse transcription‑quantitative PCR and western blotting were used to determine gene and protein expression. CCK8, wound healing, and Transwell assays were performed to evaluate cell proliferation, migration and permeability. NTN4 overexpression decreased HUVEC viability and migration. In addition, NTN4 overexpression increased the expression of VE‑cadherin and decreased the permeability of HUVECs. Subsequent studies showed that NTN4 overexpression increased the NF‑κB protein level and decreased IκB‑α protein expression in HUVECs. In HUVECs treated with NF‑κB inhibitor pyrrolidine dithiocarbamate, the expression of VE‑cadherin failed to increase with NTN4 overexpression. Taken together, the results indicated that NTN4 overexpression increased VE‑cadherin expression through the activation of the NF‑κB signaling pathway in HUVECs. The present findings revealed a novel regulatory mechanism for VE‑cadherin expression and suggested a novel avenue for future research on the role of NTN4 in endothelial barrier‑related diseases.

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