CBX4 Regulates Replicative Senescence of WI-38 Fibroblasts.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Chen, Y-H; Zhang, X; Ko, K-Y; Hsueh, M-F; Kraus, VB

Published Date

  • 2022

Published In

Volume / Issue

  • 2022 /

Start / End Page

  • 5503575 -

PubMed ID

  • 35251476

Pubmed Central ID

  • PMC8890863

Electronic International Standard Serial Number (EISSN)

  • 1942-0994

Digital Object Identifier (DOI)

  • 10.1155/2022/5503575

Language

  • eng

Conference Location

  • United States