Ulinastatin protects against lipopolysaccharide-induced cardiac microvascular endothelial cell dysfunction via downregulation of lncRNA MALAT1 and EZH2 in sepsis

  • Authors:
    • Zhaoxia Yu
    • Aisa Rayile
    • Xiangyang Zhang
    • Ying Li
    • Qiang Zhao
  • View Affiliations

  • Published online on: March 15, 2017     https://doi.org/10.3892/ijmm.2017.2920
  • Pages: 1269-1276
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Abstract

The present study aimed to evaluate the effects of ulinastatin on the permeability and apoptosis of lipopolysaccharide (LPS)-induced cardiac microvascular endothelial cells (CMVECs), and investigate its molecular mechanisms in sepsis. The sepsis rat model was induced by cecal ligation and puncture (CLP), and rat CMVECs were isolated and treated with LPS or/and ulinastatin. Then, cell permeability was evaluated by transendothelial electrical resistance, reactive oxygen species (ROS) levels were assessed by 2,7-dichlorofluorescein diacetate, cell apoptosis was detected using Annexin V-FITC apoptosis detection kit, and the expression levels of Bcl-2, Bax, caspase-3, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and EZH2 were detected by RT-qPCR and/or western blotting. In addition, the relationship of MALAT1 and EZH2 was evaluated by RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay. Compared with LPS-induced CMVECs, treatment with ulinastatin significantly reduced CMVEC permeability and the percentage of apoptotic cells, as well as an increased level of Bcl-2 and inhibited the levels of ROS, caspase-3 and Bax (all p<0.05). In addition, long non-coding RNA (lncRNA) MALAT1 was confirmed to interact with EZH2 in CMVECs. Overexpression of lncRNA MALAT1 and EZH2 was found in the hearts of the sepsis rat and LPS-induced CMVECs, while ulinastatin inhibited the upregulation of lncRNA MALAT1 and EZH2 in the LPS-induced CMVECs (all p<0.05). Ulinastatin protected against LPS-induced CMVEC cell hyperpermeability and apoptosis via downregulation of lncRNA MALAT1 and EZH2 in sepsis.
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May-2017
Volume 39 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yu Z, Rayile A, Zhang X, Li Y and Zhao Q: Ulinastatin protects against lipopolysaccharide-induced cardiac microvascular endothelial cell dysfunction via downregulation of lncRNA MALAT1 and EZH2 in sepsis. Int J Mol Med 39: 1269-1276, 2017
APA
Yu, Z., Rayile, A., Zhang, X., Li, Y., & Zhao, Q. (2017). Ulinastatin protects against lipopolysaccharide-induced cardiac microvascular endothelial cell dysfunction via downregulation of lncRNA MALAT1 and EZH2 in sepsis. International Journal of Molecular Medicine, 39, 1269-1276. https://doi.org/10.3892/ijmm.2017.2920
MLA
Yu, Z., Rayile, A., Zhang, X., Li, Y., Zhao, Q."Ulinastatin protects against lipopolysaccharide-induced cardiac microvascular endothelial cell dysfunction via downregulation of lncRNA MALAT1 and EZH2 in sepsis". International Journal of Molecular Medicine 39.5 (2017): 1269-1276.
Chicago
Yu, Z., Rayile, A., Zhang, X., Li, Y., Zhao, Q."Ulinastatin protects against lipopolysaccharide-induced cardiac microvascular endothelial cell dysfunction via downregulation of lncRNA MALAT1 and EZH2 in sepsis". International Journal of Molecular Medicine 39, no. 5 (2017): 1269-1276. https://doi.org/10.3892/ijmm.2017.2920