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KDM3A inhibition attenuates high concentration insulin‑induced vascular smooth muscle cell injury by suppressing MAPK/NF‑κB pathways

  • Authors:
    • Bo‑Fang Zhang
    • Hong Jiang
    • Jing Chen
    • Xin Guo
    • Qi Hu
    • Shuo Yang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan, Hubei 430060, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1265-1274
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    Published online on: December 29, 2017
       https://doi.org/10.3892/ijmm.2017.3351
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Abstract

Previous studies have indicated that lysine (K)‑specific demethylase 3A (KDM3A) is associated with diverse diabetes‑associated cardiovascular complications in response to high glucose levels. However, the effects of KDM3A on the pathological progression of cardiovascular injuries in response to high insulin levels remain unknown. The present study aimed to explore whether KDM3A knockdown may attenuate high insulin‑induced vascular smooth muscle cell (VSMC) dysfunction, and to further investigate the underlying mechanisms. Primary VSMCs were isolated from the thoracic aorta of Sprague‑Dawley rats. Lentiviral vectors encoding control‑small interfering (si)RNA or KDM3A‑siRNA were transduced into VSMCs for 72 h, and cells were subsequently incubated in medium containing 100 nM insulin for a further 5 days. Cellular proli­feration, migration and apoptosis were measured by Cell Counting kit‑8, Transwell chamber assay and flow cytometry, respectively. Reactive oxygen species (ROS) were detected using the dihydroethidium fluorescent probe. The mRNA expression levels of interleukin‑6 and monocyte chemotactic protein‑1 were measured by reverse transcription‑quantitative polymerase chain reaction. Furthermore, the protein expression levels of KDM3A, mitogen‑activated protein kinases (MAPKs), nuclear factor (NF)‑κB/p65, B‑cell lymphoma 2 (Bcl‑2)‑associated X protein and Bcl‑2 were evaluated by west­ern blotting. Lentivirus transduction with KDM3A‑siRNA markedly reduced the elevated expression of KDM3A induced by high insulin stimulation in VSMCs. In addition, inhibition of KDM3A significantly ameliorated insulin‑induced VSMC proliferation and migration, which was accompanied by decreased ROS levels, cell apoptosis and inflammatory cytokine levels. Furthermore, KDM3A gene silencing mitigated phosphorylation of MAPKs and NF‑κB/p65 activation. In conclusion, KDM3A inhibition may exert numerous protective effects on high insulin‑stimulated VSMCs, and the underlying mechanisms may be partly associated with inactivation of MAPK/NF‑κB signaling pathways.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang BF, Jiang H, Chen J, Guo X, Hu Q and Yang S: KDM3A inhibition attenuates high concentration insulin‑induced vascular smooth muscle cell injury by suppressing MAPK/NF‑κB pathways. Int J Mol Med 41: 1265-1274, 2018.
APA
Zhang, B., Jiang, H., Chen, J., Guo, X., Hu, Q., & Yang, S. (2018). KDM3A inhibition attenuates high concentration insulin‑induced vascular smooth muscle cell injury by suppressing MAPK/NF‑κB pathways. International Journal of Molecular Medicine, 41, 1265-1274. https://doi.org/10.3892/ijmm.2017.3351
MLA
Zhang, B., Jiang, H., Chen, J., Guo, X., Hu, Q., Yang, S."KDM3A inhibition attenuates high concentration insulin‑induced vascular smooth muscle cell injury by suppressing MAPK/NF‑κB pathways". International Journal of Molecular Medicine 41.3 (2018): 1265-1274.
Chicago
Zhang, B., Jiang, H., Chen, J., Guo, X., Hu, Q., Yang, S."KDM3A inhibition attenuates high concentration insulin‑induced vascular smooth muscle cell injury by suppressing MAPK/NF‑κB pathways". International Journal of Molecular Medicine 41, no. 3 (2018): 1265-1274. https://doi.org/10.3892/ijmm.2017.3351
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang BF, Jiang H, Chen J, Guo X, Hu Q and Yang S: KDM3A inhibition attenuates high concentration insulin‑induced vascular smooth muscle cell injury by suppressing MAPK/NF‑κB pathways. Int J Mol Med 41: 1265-1274, 2018.
APA
Zhang, B., Jiang, H., Chen, J., Guo, X., Hu, Q., & Yang, S. (2018). KDM3A inhibition attenuates high concentration insulin‑induced vascular smooth muscle cell injury by suppressing MAPK/NF‑κB pathways. International Journal of Molecular Medicine, 41, 1265-1274. https://doi.org/10.3892/ijmm.2017.3351
MLA
Zhang, B., Jiang, H., Chen, J., Guo, X., Hu, Q., Yang, S."KDM3A inhibition attenuates high concentration insulin‑induced vascular smooth muscle cell injury by suppressing MAPK/NF‑κB pathways". International Journal of Molecular Medicine 41.3 (2018): 1265-1274.
Chicago
Zhang, B., Jiang, H., Chen, J., Guo, X., Hu, Q., Yang, S."KDM3A inhibition attenuates high concentration insulin‑induced vascular smooth muscle cell injury by suppressing MAPK/NF‑κB pathways". International Journal of Molecular Medicine 41, no. 3 (2018): 1265-1274. https://doi.org/10.3892/ijmm.2017.3351
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