Regulation of microRNA-155 in endothelial inflammation by targeting nuclear factor (NF)-κB P65.

Abstract

Increasing evidences have illuminated the fundamental role of inflammation in mediating all stages of atherosclerosis. miR-155, a typical multi-functional miRNA, has recently emerged as a novel component of inflammatory signal transduction in the pathogenesis of atherosclerosis. However, little is known about whether endothelial highly expressed miR-155 can regulate endothelial inflammation-related transcription factors and the predicted role of miR-155 as a negative feedback regulator in endothelial inflammation involved in atherosclerosis. Bioinformatics analysis showed that RELA (nuclear factor-κB p65) is a potential target gene of miR-155 and this was confirmed by a luciferase reporter assay. Our results show that microRNA-155 mediate endothelial inflammation and decrease NFкB p65 and adhesion molecule expression in TNFα-stimulated endothelial cells. Transfection with miR-155 significantly inhibited TNFα-induced monocyte adhesion to endothelium. Inhibition of miR-155 enhanced p65 level and endothelial inflammatory response which was counteracted through the depletion of P65 by Si-P65. On the other hand, knockdown of eNOS, another target of miR-155, while transfecting with miR-155 inhibitor resulted in more significant inflammatory response. miR-155 is highly expressed in TNFα treated HUVECs, deprived of endogenous p65 could reverse TNFα-induced upregulation of miR-155. Thus, TNFα induced miR-155 may serve as a negative feedback regulator in endothelial inflammation involved in atherosclerosis by targeting nuclear transcription factor P65. These results provide a rationale for intervention of intracellular microRNA as possible anti-atherosclerotic targets.

• Authors: Xiao-Yuan Wu, Wen-Dong Fan, Rong Fang, Gui-Fu Wu
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 115 Issue 11 Pg. 1928-36 (Nov 2014) ISSN: 1097-4644 [Electronic] United States
• PMID: 24905663 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• 3' Untranslated Regions
• Cytokines
• MIRN155 microRNA, human
• MicroRNAs
• RELA protein, human
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha

Topics

• 3' Untranslated Regions
• Cytokines (metabolism)
• HEK293 Cells
• Human Umbilical Vein Endothelial Cells
• Humans
• Inflammation (genetics, metabolism)
• MicroRNAs (genetics, metabolism)
• Models, Biological
• Transcription Factor RelA (genetics, metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)