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

Yu,Zhaoxia; Rayile,Aisa; Zhang,Xiangyang; Li,Ying; Zhao,Qiang

doi:10.3892/ijmm.2017.2920

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
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Affiliations: Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China, Department of Cardiac Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
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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