APOC3 promotes TNF-α-induced expression of JAM-1 in endothelial cell via PI3K-IKK2-p65 pathway.

Authors:
Lu Dai
Lu Dai
Medical University of South Carolina
United States
Zhong-Hui Wang
Zhong-Hui Wang
Thermal & Environmental Engineering Institute
China
Hong-bing Ni
Hong-bing Ni
Laboratory Medicine Center; Affiliated Hospital of Nantong University
China
Xia Ding
Xia Ding
Zhejiang University
China
Yun Tao
Yun Tao
University of Chicago
United States
Ye Ding
Ye Ding
School of Public Health
China
Shao-qing Ju
Shao-qing Ju
Laboratory Medicine Center; Affiliated Hospital of Nantong University
China

Cardiovasc Pathol 2019 Jul - Aug;41:11-17. Epub 2019 Mar 4.

Department of Laboratory Medicine, Affiliated Hospital of Nantong University, 20 Xi Si Road, Nantong 226001, People's Republic of China; Insitute of Public Health, Nantong University, 9 Se Yuan Road, Nantong 226001, People's Republic of China. Electronic address:

Atherosclerosis is a chronic inflammatory disease with lipid accumulation. Apolipoprotein C3 (APOC3), which is an important regulator of human lipid metabolism, is associated with multiple vascular mechanisms in atherosclerosis and proinflammatory responses. We have previously reported that the expression of inflammatory cytokine TNF-α is elevated in human endothelial cells (HUVECs) after APOC3 treatment. This study investigates the APOC3 signaling pathway involved in TNF-α-mediated expression of JAM-1 in HUVECs. Cultured HUVECs were exposed to APOC3 (50 μg/ml) for 16 h. Mechanistic studies were carried out by silencing TNF-α gene with lentiviral TNF-α-shRNA. Our study was based on the eight signaling pathway inhibitors to block the effect of APOC3 in HUVECs. The expression of JAM-1 was determined by qRT-PCR, Western blotting, and flow cytometry. IKK2 degradation and NF-κB p65 phosphorylation were determined by Western blotting. Our results showed that APOC3 significantly promoted the TNF-α-induced expression of JAM-1 in HUVECs. Inhibiting APOC3 reversed the TNF-α-induced overexpression of JAM-1. Moreover, APOC3 induced the expression of NF-κB p65 and degraded IκB. In conclusion, APOC3 promoted the expression of JAM-1 via the NF-κB, IKK2, and PI3K signaling pathway.

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Source
https://linkinghub.elsevier.com/retrieve/pii/S10548807183031
Publisher Site
http://dx.doi.org/10.1016/j.carpath.2019.02.005DOI Listing
March 2019
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