Liver X receptor-α and miR-130a-3p regulate expression of sphingosine 1-phosphate receptor 2 in human umbilical vein endothelial cells
| Autor: | Qiaobing Huang, Xuliang Huang, Aihui Fan, Bo Chen, Yongjun Yuan, Qiang Li, Lixian Chen, Jilun Cheng, Xiaohua Guo, Qian Wang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Benzylamines Small interfering RNA Time Factors Physiology Down-Regulation Biology Transfection Benzoates Permeability Umbilical vein Tight Junctions 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Sphingosine Electric Impedance Human Umbilical Vein Endothelial Cells Humans Liver X receptor Receptor Sphingosine-1-Phosphate Receptors Cells Cultured Liver X Receptors S1PR2 Gene knockdown Tumor Necrosis Factor-alpha Cell Biology Orphan Nuclear Receptors Up-Regulation Cell biology MicroRNAs Receptors Lysosphingolipid 030104 developmental biology Biochemistry chemistry 030220 oncology & carcinogenesis Zonula Occludens-1 Protein RNA Interference Lysophospholipids Signal Transduction |
| Zdroj: | American Journal of Physiology-Cell Physiology. 310:C216-C226 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00102.2015 |
| Popis: | Recent studies have shown that activation of liver X receptors (LXRs) attenuates the development of atherosclerosis, not only by regulating lipid metabolism but also by suppressing inflammatory signaling. Sphingosine 1-phosphate receptor 2 (S1PR2), an important inflammatory gene product, plays a role in the development of various inflammatory diseases. It was proposed that S1PR2 might be regulated by LXR-α. In the present study, the effect of LXR-α on tumor necrosis factor-α (TNF-α)-induced S1PR2 expression in human umbilical vein endothelial cells (HUVECs) was investigated and the underlying mechanism was explored. The results demonstrated that TNF-α led to an increase in S1PR2 expression and triggered a downregulation of LXR-α expression in HUVECs as well. Downregulation of LXR-α with specific small interfering RNA (siRNA) remarkably enhanced the primary as well as TNF-α-induced expression of S1PR2 in HUVECs. Activation of LXR-α by agonist GW3965 inhibited both primary and TNF-α-induced S1PR2 expression. GW3965 also attenuated S1PR2-induced endothelial barrier dysfunction. The data further showed that TNF-α induced a significant decrease in miR-130a-3p expression. Overexpression of miR-130a-3p with mimic product reduced S1PR2 protein expression, and inhibition of miR-130a-3p by specific inhibitor resulted in an increase in S1PR2 protein expression. Furthermore, activation of LXRs with agonist enhanced the expression of miR-130a-3p, and knockdown of LXR-α by siRNA suppressed miR-130a-3p expression. These results suggest that LXR-α might downregulate S1PR2 expression via miR-130a-3p in quiescent HUVECs. Stimulation of TNF-α attenuates the activity of LXR-α and results in enhanced S1PR2 expression. |
| Databáze: | OpenAIRE |
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