Knockdown of Ror2 suppresses TNF‑α‑induced inflammation and apoptosis in vascular endothelial cells

Yang,Xiaohu; Zhao,Suming; Yuan,Hongxin; Shi,Rongfeng; Gu,Weiwei; Gu,Zhuxin; Lu ,Xiaohua; Zhao,Hui

doi:10.3892/mmr.2020.11377

Knockdown of Ror2 suppresses TNF‑α‑induced inflammation and apoptosis in vascular endothelial cells

Authors:
- Xiaohu Yang
- Suming Zhao
- Hongxin Yuan
- Rongfeng Shi
- Weiwei Gu
- Zhuxin Gu
- Xiaohua Lu
- Hui Zhao
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Affiliations: Department of Intervention Radiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China
Published online on: July 28, 2020 https://doi.org/10.3892/mmr.2020.11377
Pages: 2981-2989

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Abstract

Wnt family member 5a (Wnt5a) is a noncanonical member of the Wnt family that is highly expressed in atherosclerosis. Studies have shown that Wnt5a/receptor tyrosine kinase‑like orphan receptors 2 (Ror2) signaling can participate in the formation of foam cells; however, the role of Ror2 in vascular endothelial cells during atherosclerotic injury is unknown. Therefore, the present study aimed to investigate the role of Ror2 in tumor necrosis factor (TNF)‑α‑induced vascular endothelial cell injury and investigate whether it could be regulated by Wnt5a. Human umbilical vein endothelial cells were transfected with short hairpin RNA specific against Ror2 in the absence or presence of TNF‑α. The alteration of inflammatory cytokine levels was detected, and the expression of adhesion molecules was assessed. Western blot and flow cytometry analyses were used to detect the activation of nuclear factor‑κB (NF‑κB) signaling and cell apoptosis. The interaction between Ror2 and Wnt5a was confirmed by immunoprecipitation. Ror2 was upregulated upon TNF‑α stimulation. Knockdown of Ror2 inhibited the TNF‑α‑induced release of inflammatory cytokines, the expression of intercellular adhesion molecule‑1 and vascular cell adhesion molecule‑1 and the activation of NF‑κB signaling. Furthermore, cell apoptosis induced by TNF‑α was rescued by Ror2 silencing. In addition, Wnt5a expression was increased by TNF‑α, and Ror2 could bind to Wnt5a, the knockdown of which could downregulate the levels of Ror2. In conclusion, it was demonstrated that Ror2 was upregulated upon TNF‑α stimuli, and interference of Ror2 regulated by Wnt5a could suppress TNF‑α‑induced inflammation and apoptosis in vascular endothelial cells.

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