MiR-130b attenuates vascular inflammation via negatively regulating tumor progression locus 2 (Tpl2) expression

• Published in: International immunopharmacology 2017-10, Vol.51, p.9-16
• Main Authors: Wang, Peng, Zhang, Xue, Li, Fulun, Yuan, Kai, Li, Maoran, Zhang, Jiwei, Li, Bin, Liang, Wei
• Format: Article
• Language: English
• Subjects: Animals; Cell activation; Disease Models, Animal; Endothelial cell; Endothelial cells; Endothelium; Endothelium, Vascular - physiology; Extracellular signal-regulated kinase; Gene expression; Human Umbilical Vein Endothelial Cells; Humans; Inflammation - immunology; Inflammatory diseases; Interleukin-6 - metabolism; Interleukins; Lipopolysaccharides; Lipopolysaccharides - immunology; Loci; Lungs; Male; MAP Kinase Kinase Kinases - genetics; MAP Kinase Kinase Kinases - metabolism; Medical treatment; Mice; Mice, Inbred C57BL; microRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Sepsis; Sepsis - immunology; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Umbilical vein
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2017.07.020

Endothelial cell (EC) activation and dysfunction have been linked to a wide variety of vascular inflammatory diseases. However, the role of microRNAs in EC activation and inflammation remains largely unknown. In this study, we found that miR-130b was significantly decreased in human umbilical vein endothelial cells (HUVECs) after lipopolysaccharides (LPS) treatment. Forced expression of miR-130b inhibited the LPS-induced activation of extracellular signal-regulated kinase (ERK) and the inflammatory genes expression, such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α). Furthermore, we identified that tumor progression locus 2 (Tpl2) is a direct target of miR-130b. Finally, in vivo overexpression of miR-130b via miR-130b agomir attenuates acute lung vascular inflammation in the LPS-induced sepsis mouse model. Taken together, our data demonstrated that miR-130b represses vascular inflammation via targeting Tpl2, suggesting that miR-130b mimics might be a promising therapeutic strategy for treatment of vascular inflammatory diseases. [Display omitted] •miR-130b is significantly reduced in HUVECs after LPS treatment.•miR-130b inhibits inflammation related gene expression.•miR-130b inhibits ERK activation via negatively regulating TPL2 expression.•In vivo overexpression of miR-130b attenuates LPS-induced vascular inflammation.