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Article Open Access

EZH2 inhibitor GSK343 inhibits sepsis‑induced intestinal disorders

  • Authors:
    • Dongyou Yue
    • Zhiying Wang
    • Yongan Yang
    • Zhenjun Hu
    • Ganping Luo
    • Fu Wang
  • View Affiliations / Copyright

    Affiliations: Department of Emergency, The First People's Hospital of Chenzhou City, Chenzhou, Hunan 423000, P.R. China, Department of Neurology, The First People's Hospital of Chenzhou City, Chenzhou, Hunan 423000, P.R. China, Department of Critical Care Medicine, Zhangye Second People's Hospital, Zhangye, Gansu 734000, P.R. China
    Copyright: © Yue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 437
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    Published online on: February 26, 2021
       https://doi.org/10.3892/etm.2021.9854
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Abstract

Enhancer of zeste homolog 2 (EZH2) is positively associated with poor clinical outcomes in a number of aggressive tumors. Recent studies have demonstrated that inhibition of EZH2 also suppressed the inflammatory response during sepsis. The present study aimed to investigate whether an inhibitor of EZH2, GSK343, could protect the intestine against sepsis‑induced injury in vivo. Mice underwent cecal ligation and perforation (CLP) to induce sepsis and were assigned into three groups: Sham, CLP and CLP + GSK343. For GSK343 treatment, the septic mice were intravenously injected with GSK343 at 6 h post‑CLP. The results indicated that EZH2 was highly expressed while tight junction (TJ) proteins ZO‑1, occludin and claudin‑1 expression was reduced in the intestinal tissue of mice subjected to CLP compared with the sham group. CLP operation also caused intestinal pathological injury and the production of inflammatory cytokines including TNF‑α, IL‑1β and IL‑6 in both serum and intestinal tissues. Meanwhile, CLP induced cell apoptosis of intestinal tissue based on the increased number of apoptotic cells, reduced expression of Bcl‑2 and higher expression of caspase‑3 and Bax. However, the presence of GSK343 partially rescued intestinal pathological injury, reduced the level of inflammatory cytokines, repressed cell apoptosis and promoted TJ protein expression. Finally, the decreased number of Paneth cells caused by CLP operation was reversed by GSK343 treatment. In conclusion, the results of the present study demonstrated that GSK343 could protect the intestine against sepsis‑induced injury in vivo. Inhibition of EZH2 may provide a therapeutic approach for intestinal dysfunction during sepsis.
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Copy and paste a formatted citation
Spandidos Publications style
Yue D, Wang Z, Yang Y, Hu Z, Luo G and Wang F: EZH2 inhibitor GSK343 inhibits sepsis‑induced intestinal disorders. Exp Ther Med 21: 437, 2021.
APA
Yue, D., Wang, Z., Yang, Y., Hu, Z., Luo, G., & Wang, F. (2021). EZH2 inhibitor GSK343 inhibits sepsis‑induced intestinal disorders. Experimental and Therapeutic Medicine, 21, 437. https://doi.org/10.3892/etm.2021.9854
MLA
Yue, D., Wang, Z., Yang, Y., Hu, Z., Luo, G., Wang, F."EZH2 inhibitor GSK343 inhibits sepsis‑induced intestinal disorders". Experimental and Therapeutic Medicine 21.5 (2021): 437.
Chicago
Yue, D., Wang, Z., Yang, Y., Hu, Z., Luo, G., Wang, F."EZH2 inhibitor GSK343 inhibits sepsis‑induced intestinal disorders". Experimental and Therapeutic Medicine 21, no. 5 (2021): 437. https://doi.org/10.3892/etm.2021.9854
Copy and paste a formatted citation
x
Spandidos Publications style
Yue D, Wang Z, Yang Y, Hu Z, Luo G and Wang F: EZH2 inhibitor GSK343 inhibits sepsis‑induced intestinal disorders. Exp Ther Med 21: 437, 2021.
APA
Yue, D., Wang, Z., Yang, Y., Hu, Z., Luo, G., & Wang, F. (2021). EZH2 inhibitor GSK343 inhibits sepsis‑induced intestinal disorders. Experimental and Therapeutic Medicine, 21, 437. https://doi.org/10.3892/etm.2021.9854
MLA
Yue, D., Wang, Z., Yang, Y., Hu, Z., Luo, G., Wang, F."EZH2 inhibitor GSK343 inhibits sepsis‑induced intestinal disorders". Experimental and Therapeutic Medicine 21.5 (2021): 437.
Chicago
Yue, D., Wang, Z., Yang, Y., Hu, Z., Luo, G., Wang, F."EZH2 inhibitor GSK343 inhibits sepsis‑induced intestinal disorders". Experimental and Therapeutic Medicine 21, no. 5 (2021): 437. https://doi.org/10.3892/etm.2021.9854
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