Role of DNA damage in the progress of chronic tubule‑interstitial injury

  • Authors:
    • Linxiao Sun
    • Xiandong Zhu
    • Jiao Luo
    • Cheng Wang
    • Bicheng Chen
  • View Affiliations

  • Published online on: May 14, 2020     https://doi.org/10.3892/mmr.2020.11146
  • Pages: 1081-1089
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Abstract

Tubulointerstitial fibrosis (TIF) is a common final endpoint of chronic allograft nephropathy. Over the years, several hypotheses have been developed to explain the progression of TIF, including mechanisms such as inflammation, epithelial‑mesenchymal transition, senescence, chronic hypoxia and reactive oxygen species. Furthermore, TIF is reportedly induced by the ‘damage‑proliferation‑death’ cycle. In the present study, an AA renal fibrosis model was established in vitro to investigate whether the vicious proliferation‑death cycle is a pathophysiological process of TIF following chronic injury to the kidneys. Results from the present study revealed that cell death was associated with the entrance of cells into the cell cycle. Genetic knockdown of p21 was observed to increase cell cycle progression and the proliferative rate of cells, which overall promoted increased rates of cell death. In addition, the activation of the DNA damage response (DDR) signaling pathway was demonstrated to be crucial to the initiation of the vicious cycle of ‘proliferation‑death’. Ataxia telangiectasia mutated (ATM) is an important molecule of the DDR and the genetic knockdown of ATM induced apoptosis, increased cell proliferation and promoted cell death. The increase in apoptosis was suggested to be due to the decreased expression levels of p21 observed following the genetic knockdown of ATM. In conclusion, the present study suggested that the crosstalk between the ATM and p21 protein may serve an important role in the regulation of the ‘proliferation‑death’ cycle in the progress of chronic tubulointerstitial injury.

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August-2020
Volume 22 Issue 2

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

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APA
Sun, L., Zhu, X., Luo, J., Wang, C., & Chen, B. (2020). Role of DNA damage in the progress of chronic tubule‑interstitial injury. Molecular Medicine Reports, 22, 1081-1089. https://doi.org/10.3892/mmr.2020.11146
MLA
Sun, L., Zhu, X., Luo, J., Wang, C., Chen, B."Role of DNA damage in the progress of chronic tubule‑interstitial injury". Molecular Medicine Reports 22.2 (2020): 1081-1089.
Chicago
Sun, L., Zhu, X., Luo, J., Wang, C., Chen, B."Role of DNA damage in the progress of chronic tubule‑interstitial injury". Molecular Medicine Reports 22, no. 2 (2020): 1081-1089. https://doi.org/10.3892/mmr.2020.11146