ox-LDL increases microRNA-29a transcription through upregulating YY1 and STAT1 in macrophages.
Macrophages and oxidized low-density lipoprotein (ox-LDL) have been verified playing vital roles in the pathogenesis of atherosclerosis (AS). Previous studies demonstrated that microRNA-29a (miR-29a) was upregulated in many atherogenic process and cells, thus acting as an important participant in AS. But the detailed regulation mechanism of miR-29a in AS has not been fully understood. In our study, we demonstrated a positive feedback loop of ox-LDL-SRA-miR-29a. Furthermore, we found that YY1 and STAT1 were upregulated in ox-LDL-stimulating macrophages followed by translocation in the nucleus and binding to the transcriptional promoter region of miR-29a, thus leading to the increase of miR-29a expression. In addition, we demonstrated that JAK1/2 signaling was involved in miR-29a upregulation. Finally, we found that miR-29a played important roles in the secretion of proinflammation factors and lipid uptake in macrophages. We uncovered the molecular mechanism and provide novel insights into the function and regulatory network of miR-29a expression regulated by ox-LDL in macrophages.
['Jian|Dongdong|D|', 'Dai|Bing|B|', 'Hu|Xiaotong|X|', 'Yao|Qiang|Q|', 'Zheng|Chengfei|C|', 'Zhu|Jianhua|J|']
D050197:Atherosclerosis D006801:Humans D008077:Lipoproteins, LDL D008264:Macrophages D035683:MicroRNAs D050794:STAT1 Transcription Factor D051117:Scavenger Receptors, Class A D015398:Signal Transduction D000074084:THP-1 Cells D015533:Transcriptional Activation D015854:Up-Regulation D050986:YY1 Transcription Factor
ox-LDL YY1 STAT1 macrophages miR-29a