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Article

Effects of the p16/cyclin D1/CDK4/Rb/E2F1 pathway on aberrant lung fibroblast proliferation in neonatal rats exposed to hyperoxia

  • Authors:
    • Shimeng Zhao
    • Zhiguang Chen
    • Shuang Han
    • Hongmin Wu
  • View Affiliations / Copyright

    Affiliations: Department of Neonatology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
  • Article Number: 1057
    |
    Published online on: July 26, 2021
       https://doi.org/10.3892/etm.2021.10491
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Abstract

p16INK4a (p16) inhibits the vital G1 to S phase transition during cell cycle progression through the p16/cyclin D1/CDK4/retinoblastoma(Rb)/E2F1 pathway. Hyperoxia can suppress the G1/S checkpoint and induce more lung fibroblasts (LFs) to transition from the G1 phase to the S phase and undergo cell proliferation. The present study investigated the rate of p16 gene promoter methylation and the protein expression levels of p16, cyclin D1, CDK4, Rb and E2F1 in LFs from the lungs of rats exposed to hyperoxia and normoxia on postnatal days 3, 7 and 14. In the hyperoxia‑exposed group, the methylation rate was 50 and 80% on days 7 and 14, respectively. Cyclin D1 and CDK4 overexpression was associated with p16 loss and Rb inactivation by phosphorylation. Rb phosphorylation induced E2F1 release in the G1 phase, which promoted cell proliferation. No methylation was observed in the normoxia‑exposed group. These observations suggested that p16 loss may stimulate aberrant LF proliferation via the p16/cyclin D1/CDK4/Rb/E2F1 pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao S, Chen Z, Han S and Wu H: Effects of the p16/cyclin D1/CDK4/Rb/E2F1 pathway on aberrant lung fibroblast proliferation in neonatal rats exposed to hyperoxia. Exp Ther Med 22: 1057, 2021.
APA
Zhao, S., Chen, Z., Han, S., & Wu, H. (2021). Effects of the p16/cyclin D1/CDK4/Rb/E2F1 pathway on aberrant lung fibroblast proliferation in neonatal rats exposed to hyperoxia. Experimental and Therapeutic Medicine, 22, 1057. https://doi.org/10.3892/etm.2021.10491
MLA
Zhao, S., Chen, Z., Han, S., Wu, H."Effects of the p16/cyclin D1/CDK4/Rb/E2F1 pathway on aberrant lung fibroblast proliferation in neonatal rats exposed to hyperoxia". Experimental and Therapeutic Medicine 22.4 (2021): 1057.
Chicago
Zhao, S., Chen, Z., Han, S., Wu, H."Effects of the p16/cyclin D1/CDK4/Rb/E2F1 pathway on aberrant lung fibroblast proliferation in neonatal rats exposed to hyperoxia". Experimental and Therapeutic Medicine 22, no. 4 (2021): 1057. https://doi.org/10.3892/etm.2021.10491
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao S, Chen Z, Han S and Wu H: Effects of the p16/cyclin D1/CDK4/Rb/E2F1 pathway on aberrant lung fibroblast proliferation in neonatal rats exposed to hyperoxia. Exp Ther Med 22: 1057, 2021.
APA
Zhao, S., Chen, Z., Han, S., & Wu, H. (2021). Effects of the p16/cyclin D1/CDK4/Rb/E2F1 pathway on aberrant lung fibroblast proliferation in neonatal rats exposed to hyperoxia. Experimental and Therapeutic Medicine, 22, 1057. https://doi.org/10.3892/etm.2021.10491
MLA
Zhao, S., Chen, Z., Han, S., Wu, H."Effects of the p16/cyclin D1/CDK4/Rb/E2F1 pathway on aberrant lung fibroblast proliferation in neonatal rats exposed to hyperoxia". Experimental and Therapeutic Medicine 22.4 (2021): 1057.
Chicago
Zhao, S., Chen, Z., Han, S., Wu, H."Effects of the p16/cyclin D1/CDK4/Rb/E2F1 pathway on aberrant lung fibroblast proliferation in neonatal rats exposed to hyperoxia". Experimental and Therapeutic Medicine 22, no. 4 (2021): 1057. https://doi.org/10.3892/etm.2021.10491
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