Open Access

Effect of KNDC1 overexpression on the senescence of human umbilical vein endothelial cells

  • Authors:
    • Jinrui Ji
    • Zhenxuan Hao
    • Hengliang Liu
    • Yang Liu
    • Jing Liu
    • Binghui Lin
    • Chao Ma
    • Yajun Lin
  • View Affiliations

  • Published online on: March 19, 2018     https://doi.org/10.3892/mmr.2018.8775
  • Pages: 7037-7044
  • Copyright: © Ji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Kinase non-catalytic C-lobe domain containing 1 (KNDC1) exists in dendrites, guanine nucleotide exchange factor complexes and neuronal cell bodies as a putative protein‑protein interaction module that regulates a number of signaling pathways. Previous studies have demonstrated that the knockdown of KNDC1 delays human umbilical vein endothelial cell (HUVEC) senescence. However, the effect of KNDC1 overexpression on HUVEC function remains unclear. In the present study, an adenovirus vector carrying KNDC1 was constructed and then transfected into endothelial cells to observe cell senescence. Furthermore, the effect of KNDC1 overexpression on HUVEC senescence was investigated in vitro and the underlying molecular mechanism was investigated. Senescence‑associated β‑galactosidase staining was used to determine cellular senescence and reactive oxygen species (ROS) were monitored to detect the level of cell oxidative stress. The mRNA transcription level and protein expression were analyzed by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. The results demonstrated that KNDC1 overexpression possibly inhibited HUVEC activity and function and promoted HUVEC senescence. Mechanistic studies demonstrated that KNDC1 triggered a p53‑ROS positive feedback loop, which serves a crucial role in regulating senescence. In conclusion, to the best of the authors' knowledge, this is the first time that KNDC1‑adenovirus vector inhibition of HUVEC proliferation by activating the p53 signaling pathway has been reported. Theoretically, the results of the present study also support KNDC1 as a therapeutic target for future anti-senescence.
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May-2018
Volume 17 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Ji J, Hao Z, Liu H, Liu Y, Liu J, Lin B, Ma C and Lin Y: Effect of KNDC1 overexpression on the senescence of human umbilical vein endothelial cells. Mol Med Rep 17: 7037-7044, 2018
APA
Ji, J., Hao, Z., Liu, H., Liu, Y., Liu, J., Lin, B. ... Lin, Y. (2018). Effect of KNDC1 overexpression on the senescence of human umbilical vein endothelial cells. Molecular Medicine Reports, 17, 7037-7044. https://doi.org/10.3892/mmr.2018.8775
MLA
Ji, J., Hao, Z., Liu, H., Liu, Y., Liu, J., Lin, B., Ma, C., Lin, Y."Effect of KNDC1 overexpression on the senescence of human umbilical vein endothelial cells". Molecular Medicine Reports 17.5 (2018): 7037-7044.
Chicago
Ji, J., Hao, Z., Liu, H., Liu, Y., Liu, J., Lin, B., Ma, C., Lin, Y."Effect of KNDC1 overexpression on the senescence of human umbilical vein endothelial cells". Molecular Medicine Reports 17, no. 5 (2018): 7037-7044. https://doi.org/10.3892/mmr.2018.8775