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KNDC1 knockdown protects human umbilical vein endothelial cells from senescence

  • Authors:
    • Chunyan Zhang
    • Yong-Zhan Zhen
    • Ya-Jun Lin
    • Jiang Liu
    • Jie Wei
    • Rong Xu
    • Gang Hu
  • View Affiliations / Copyright

    Affiliations: Radiologic Department, Beijing Shijitan Hospital Affiliated of Capital Medical University, Beijing 100038, P.R. China, Department of Histology and Embryology, Basic Medical College of Hebei United University, Tangshan, Hebei 063000, P.R. China, Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, P.R. China, Department of Endocrinology, The Third Hospital of Nanchang City, Nanchang, Jiangxi 330009, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 82-88
    |
    Published online on: April 30, 2014
       https://doi.org/10.3892/mmr.2014.2201
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Abstract

KNDC1 (kinase noncatalytic C-lobe domain containing 1), a brain-specific Ras guanine nucleotide exchange factor, controls the negative regulation of neuronal dendrite growth. However, the effect of KNDC1 on cellular senescence remains to be elucidated. The present study investigated the impact of KNDC1 knockdown on human endothelial cell senescence and the mechanisms underlying this effect. Human umbilical vein endothelial cells (HUVECs) cultured in vitro were used as a model of biological aging. Senescence‑associated β-galactosidase staining was used to detect cellular senescence and flow cytometry was employed to determine cell cycle progression. Quantitative polymerase chain reaction (qPCR) and western blot analysis were utilized to investigate mRNA transcription and protein expression. In the HUVECs, a senescence-like phenotypes developed with increasing passage number in vitro, which were associated with a progressive increase in the transcription and expression of KNDC1. KNDC1 knockdown promoted cell proliferation and partially reversed cellular senescence and cell cycle arrest in the G0/G1 phase in aging HUVECs. Investigations into the mechanism underlying this effect demonstrated that KNDC1 knockdown promoted HUVEC proliferation via the extracellular signal-regulated kinase signaling pathway and delayed HUVEC senescence by inhibiting the p53-p21-p16 transduction cascade. In addition, the promotion of the capillary tube network formation and the increased expression of endothelial nitric oxide synthase revealed that the activity and function of endothelial cells were enhanced. In conclusion, KNDC1 knockdown delayed endothelial cell senescence and promoted HUVEC activity and function. These results demonstrated that KNDC1 may be a novel therapeutic target for the development of agents to extend human life.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang C, Zhen Y, Lin Y, Liu J, Wei J, Xu R and Hu G: KNDC1 knockdown protects human umbilical vein endothelial cells from senescence. Mol Med Rep 10: 82-88, 2014.
APA
Zhang, C., Zhen, Y., Lin, Y., Liu, J., Wei, J., Xu, R., & Hu, G. (2014). KNDC1 knockdown protects human umbilical vein endothelial cells from senescence. Molecular Medicine Reports, 10, 82-88. https://doi.org/10.3892/mmr.2014.2201
MLA
Zhang, C., Zhen, Y., Lin, Y., Liu, J., Wei, J., Xu, R., Hu, G."KNDC1 knockdown protects human umbilical vein endothelial cells from senescence". Molecular Medicine Reports 10.1 (2014): 82-88.
Chicago
Zhang, C., Zhen, Y., Lin, Y., Liu, J., Wei, J., Xu, R., Hu, G."KNDC1 knockdown protects human umbilical vein endothelial cells from senescence". Molecular Medicine Reports 10, no. 1 (2014): 82-88. https://doi.org/10.3892/mmr.2014.2201
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang C, Zhen Y, Lin Y, Liu J, Wei J, Xu R and Hu G: KNDC1 knockdown protects human umbilical vein endothelial cells from senescence. Mol Med Rep 10: 82-88, 2014.
APA
Zhang, C., Zhen, Y., Lin, Y., Liu, J., Wei, J., Xu, R., & Hu, G. (2014). KNDC1 knockdown protects human umbilical vein endothelial cells from senescence. Molecular Medicine Reports, 10, 82-88. https://doi.org/10.3892/mmr.2014.2201
MLA
Zhang, C., Zhen, Y., Lin, Y., Liu, J., Wei, J., Xu, R., Hu, G."KNDC1 knockdown protects human umbilical vein endothelial cells from senescence". Molecular Medicine Reports 10.1 (2014): 82-88.
Chicago
Zhang, C., Zhen, Y., Lin, Y., Liu, J., Wei, J., Xu, R., Hu, G."KNDC1 knockdown protects human umbilical vein endothelial cells from senescence". Molecular Medicine Reports 10, no. 1 (2014): 82-88. https://doi.org/10.3892/mmr.2014.2201
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