MiR-4505 aggravates lipopolysaccharide-induced vascular endothelial injury by targeting heat shock protein A12B

Zhang,Xu; Chen,Yi; Wang,Lei; Kang,Qiuxiang; Yu,Guifang; Wan,Xiaojian; Wang,Jiafeng; Zhu,Keming

doi:10.3892/mmr.2017.7936

MiR-4505 aggravates lipopolysaccharide-induced vascular endothelial injury by targeting heat shock protein A12B

Authors:
- Xu Zhang
- Yi Chen
- Lei Wang
- Qiuxiang Kang
- Guifang Yu
- Xiaojian Wan
- Jiafeng Wang
- Keming Zhu
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Affiliations: Department of Anesthesiology and Intensive Care Medicine, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China, Department of Anesthesiology, The Third People's Hospital, Shanghai Jiaotong University, Shanghai 201999, P.R. China
Published online on: November 2, 2017 https://doi.org/10.3892/mmr.2017.7936
Pages: 1389-1395

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Abstract

Heat shock protein family A member 12B (HSPA12B) is a heat shock protein primarily expressed in endothelial cells. Our previous study showed that it was protective against endothelial injury induced by lipopolysaccharide (LPS). The present study was performed to investigate whether micro (mi)RNA was involved in HSPA12B expression in endothelial cells challenged by LPS. We first screened the miRNA candidates potentially related to HSPA12B by bioinformatics analysis. Then the mimics of the miRNA candidates were transfected into human umbilical vein endothelial cells (HUVECs) to investigate the miRNAs that negatively regulated HSPA12B expression. The miRNA expression was also determined in LPS‑stimulated HUVECs. Dual luciferase activity assay was performed to confirm the relationship between the candidate miRNA and HSPA12B. Role of nuclear factor (NF)‑κB in the miRNA expression was investigated by using its inhibitor. Finally, the role of the miRNA on LPS induced injury was investigated. Eleven miRNAs were screened by bioinformatics analysis and 4 of them could inhibit HSPA12B expression at both mRNA and protein levels. Among the 4 miRNA candidates, only miR‑4505 was highly expressed in HUVECs stimulated by LPS. Luciferase analysis showed that miR‑4505 directly interacted with the 3'untranslated region of HSPA12B. LPS‑induced upregulation of miR‑4505 was blocked by NF‑κB inhibitor. Transfection with miR‑4505 mimics reduced the transendothelial electrical resistance and vascular endothelial‑cadherin expression. The scratch test demonstrated that miR‑4505 inhibited endothelial migration capacity. In conclusion, miR‑4505 downregulates the expression of HSPA12B and aggravates the LPS‑induced vascular endothelial cell injury.

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