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CBX4 Regulates Replicative Senescence of WI-38 Fibroblasts.

Publication ,  Journal Article
Chen, Y-H; Zhang, X; Ko, K-Y; Hsueh, M-F; Kraus, VB
Published in: Oxid Med Cell Longev
2022

Cellular senescence is characterized by cell cycle arrest and senescence-associated secretory phenotypes. Cellular senescence can be caused by various stress stimuli such as DNA damage, oxidative stress, and telomere attrition and is related to several chronic diseases, including atherosclerosis, Alzheimer's disease, and osteoarthritis. Chromobox homolog 4 (CBX4) has been shown to alleviate cellular senescence in human mesenchymal stem cells and is considered a possible target for senomorphic treatment. Here, we explored whether CBX4 expression is associated with replicative senescence in WI-38 fibroblasts, a classic human senescence model system. We also examined whether and how regulation of CBX4 modifies the senescence phenotype and functions as an antisenescence target in WI-38. During the serial culture of the WI-38 primary fibroblast cell line to a senescent state, we found increased expression of senescence markers, including senescence β-galactosidase (SA-βgal) activity, protein expression of p16, p21, and DPP4, and decreased proliferation marker EdU; moreover, CBX4 protein expression declined. With knockdown of CBX4, SA-βgal activity and p16 protein expression increased, and EdU decreased. With the activation of CBX4, SA-βgal activity, p16, and DPP4 protein decreased. In addition, CBX4 knockdown increased, while CBX4 activation decreased, gene expression of both CDKN2A (encoding the p16 protein) and DPP4. Genes related to DNA damage and cell cycle pathways were regulated by CBX4. These results demonstrate that CBX4 can regulate replicative senescence in a manner consistent with a senomorphic agent.

Duke Scholars

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Published In

Oxid Med Cell Longev

DOI

EISSN

1942-0994

Publication Date

2022

Volume

2022

Start / End Page

5503575

Location

United States

Related Subject Headings

  • beta-Galactosidase
  • Transduction, Genetic
  • Signal Transduction
  • Polycomb-Group Proteins
  • Phenotype
  • Oxidative Stress
  • Ligases
  • Humans
  • Gene Knockdown Techniques
  • Gene Expression Regulation
 

Citation

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ICMJE
MLA
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Chen, Y.-H., Zhang, X., Ko, K.-Y., Hsueh, M.-F., & Kraus, V. B. (2022). CBX4 Regulates Replicative Senescence of WI-38 Fibroblasts. Oxid Med Cell Longev, 2022, 5503575. https://doi.org/10.1155/2022/5503575
Chen, Yu-Hsiu, Xin Zhang, Kuei-Yueh Ko, Ming-Feng Hsueh, and Virginia Byers Kraus. “CBX4 Regulates Replicative Senescence of WI-38 Fibroblasts.Oxid Med Cell Longev 2022 (2022): 5503575. https://doi.org/10.1155/2022/5503575.
Chen Y-H, Zhang X, Ko K-Y, Hsueh M-F, Kraus VB. CBX4 Regulates Replicative Senescence of WI-38 Fibroblasts. Oxid Med Cell Longev. 2022;2022:5503575.
Chen, Yu-Hsiu, et al. “CBX4 Regulates Replicative Senescence of WI-38 Fibroblasts.Oxid Med Cell Longev, vol. 2022, 2022, p. 5503575. Pubmed, doi:10.1155/2022/5503575.
Chen Y-H, Zhang X, Ko K-Y, Hsueh M-F, Kraus VB. CBX4 Regulates Replicative Senescence of WI-38 Fibroblasts. Oxid Med Cell Longev. 2022;2022:5503575.

Published In

Oxid Med Cell Longev

DOI

EISSN

1942-0994

Publication Date

2022

Volume

2022

Start / End Page

5503575

Location

United States

Related Subject Headings

  • beta-Galactosidase
  • Transduction, Genetic
  • Signal Transduction
  • Polycomb-Group Proteins
  • Phenotype
  • Oxidative Stress
  • Ligases
  • Humans
  • Gene Knockdown Techniques
  • Gene Expression Regulation