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Article Open Access

c‑Jun/Ap‑1 is upregulated in an Ang II‑induced abdominal aortic aneurysm formation model and mediates Chop expression in mouse aortic smooth muscle cells

  • Authors:
    • Dating Sun
    • Mingxi Zhang
    • Yuanyuan Li
    • Shuai Mei
    • Jin Qin
    • Jiangtao Yan
  • View Affiliations / Copyright

    Affiliations: Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Division of Cardiology, Department of Internal Medicine, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430030, P.R. China
    Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3459-3468
    |
    Published online on: March 12, 2019
       https://doi.org/10.3892/mmr.2019.10017
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Abstract

Abdominal aortic aneurysm (AAA) is an asymptomatic, potentially lethal disease whose ruptures have a high mortality rate. An effective pharmacological approach to decrease expansion or prevent the rupture of AAAs in humans remains lacking. Previous studies have suggested that activator protein 1 (c‑Jun/AP‑1) and C/EBP homologous protein (Chop) are involved in the development of AAA. The purpose of the present study was to investigate whether c‑Jun/AP‑1 mediates Chop overexpression in AAA. c‑Jun/AP‑1 and Chop protein levels were determined in an angiotensin II (Ang II)‑induced AAA model using apolipoprotein E‑deficient mice. Additionally, mouse aortic smooth muscle cells (MOVAS cell line) were treated with Ang II. Apoptosis was evaluated via TUNEL assay, MOVAS cell migration ability was assessed by monolayer wound healing assay and the levels of c‑Jun/AP‑1 and Chop were determined by western blotting, immunofluorescence and immunocytochemical assays. Following c‑Jun silencing using c‑Jun‑specific small interfering (si)RNA, Chop expression was evaluated. Furthermore, chromatin immunoprecipitation (ChIP) was used to investigate whether c‑Jun/Ap‑1 binds directly to the DNA damage‑inducible transcript 3 protein (Ddit3) promoter. It was observed that c‑Jun/AP‑1 and Chop were synchronously overexpressed in Ang II‑induced AAA and Ang II‑treated cells, and that apoptosis and migration were induced by Ang II. In addition, Chop was suppressed when c‑Jun was silenced by targeted siRNA. Notably, the ChIP assay demonstrated that the DNA fragments pulled down by primary antibodies against c‑Jun/Ap‑1 were able to be amplified by (Ddit3) promoter‑specific primers. c‑Jun/AP‑1 may therefore mediate Chop expression in MOVAS cells via Ddit3. These results suggested that c‑Jun/AP‑1 may be a novel target for AAA therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Sun D, Zhang M, Li Y, Mei S, Qin J and Yan J: c‑Jun/Ap‑1 is upregulated in an Ang II‑induced abdominal aortic aneurysm formation model and mediates Chop expression in mouse aortic smooth muscle cells. Mol Med Rep 19: 3459-3468, 2019.
APA
Sun, D., Zhang, M., Li, Y., Mei, S., Qin, J., & Yan, J. (2019). c‑Jun/Ap‑1 is upregulated in an Ang II‑induced abdominal aortic aneurysm formation model and mediates Chop expression in mouse aortic smooth muscle cells. Molecular Medicine Reports, 19, 3459-3468. https://doi.org/10.3892/mmr.2019.10017
MLA
Sun, D., Zhang, M., Li, Y., Mei, S., Qin, J., Yan, J."c‑Jun/Ap‑1 is upregulated in an Ang II‑induced abdominal aortic aneurysm formation model and mediates Chop expression in mouse aortic smooth muscle cells". Molecular Medicine Reports 19.5 (2019): 3459-3468.
Chicago
Sun, D., Zhang, M., Li, Y., Mei, S., Qin, J., Yan, J."c‑Jun/Ap‑1 is upregulated in an Ang II‑induced abdominal aortic aneurysm formation model and mediates Chop expression in mouse aortic smooth muscle cells". Molecular Medicine Reports 19, no. 5 (2019): 3459-3468. https://doi.org/10.3892/mmr.2019.10017
Copy and paste a formatted citation
x
Spandidos Publications style
Sun D, Zhang M, Li Y, Mei S, Qin J and Yan J: c‑Jun/Ap‑1 is upregulated in an Ang II‑induced abdominal aortic aneurysm formation model and mediates Chop expression in mouse aortic smooth muscle cells. Mol Med Rep 19: 3459-3468, 2019.
APA
Sun, D., Zhang, M., Li, Y., Mei, S., Qin, J., & Yan, J. (2019). c‑Jun/Ap‑1 is upregulated in an Ang II‑induced abdominal aortic aneurysm formation model and mediates Chop expression in mouse aortic smooth muscle cells. Molecular Medicine Reports, 19, 3459-3468. https://doi.org/10.3892/mmr.2019.10017
MLA
Sun, D., Zhang, M., Li, Y., Mei, S., Qin, J., Yan, J."c‑Jun/Ap‑1 is upregulated in an Ang II‑induced abdominal aortic aneurysm formation model and mediates Chop expression in mouse aortic smooth muscle cells". Molecular Medicine Reports 19.5 (2019): 3459-3468.
Chicago
Sun, D., Zhang, M., Li, Y., Mei, S., Qin, J., Yan, J."c‑Jun/Ap‑1 is upregulated in an Ang II‑induced abdominal aortic aneurysm formation model and mediates Chop expression in mouse aortic smooth muscle cells". Molecular Medicine Reports 19, no. 5 (2019): 3459-3468. https://doi.org/10.3892/mmr.2019.10017
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