OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of MMP-2/MMP-9 genes: A novel mechanism for cardiovascular diseases

Ku Chung Chen, Yung Song Wang, Ching Yu Hu, Wei Chiao Chang, Yi Chu Liao, Chia Yen Dai, Suh Hang Hank Juo

研究成果: 雜誌貢獻文章同行評審

178 引文 斯高帕斯(Scopus)

摘要

MicroRNAs (miRNAs), small noncoding RNAs, can control gene expression by binding to their target genes for degradation and/or translational repression. Epigenetic mechanisms are defined as heritable changes in gene expression that do not involve coding sequence modifications. Both mechanisms play an important role in maintaining physiological functions and are also related to disease development. However, few studies report that miRNA-mediated epigenetic regulations are involved in atherosclerosis. In the present study, oxidized low-density lipoprotein (oxLDL) significantly increased primary human aortic smooth muscle cell (HASMC) migration through MMP-2/MMP-9 upregulation associated with decreased DNA methylation levels. Either mRNA or protein level of DNA methyltransferase 3b (DNMT3b) showed a dose-dependent down-regulation in oxLDL-mediated HASMCs. Knockdown DNMT3b expression enhanced oxLDL-induced DNA demethylation levels of MMP-2/MMP-9. The expression of miRNA-29b (miR-29b), directly targeting DNMT3b, was up-regulated by oxLDL treatment in a dose-dependent manner. OxLDL-mediated MMP-2/MMP-9 up-regulation, DNMT3b down-regulation, and DNA demethylation were all attenuated after knockdown miR-29b expression by antagomiR-29b. We find that oxLDL can up-regulate miR-29b expression, resulting in DNMT3b downregulation in HASMCs and epigenetically regulated MMP-2/MMP-9 genes involved in cell migration. These results show that miRNA-mediated epigenetic regulation may be a novel mechanism in atherosclerosis.

原文英語
頁(從 - 到)1718-1728
頁數11
期刊FASEB Journal
25
發行號5
DOIs
出版狀態已發佈 - 五月 2011
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 生物技術
  • 遺傳學
  • 分子生物學

指紋

深入研究「OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of MMP-2/MMP-9 genes: A novel mechanism for cardiovascular diseases」主題。共同形成了獨特的指紋。

引用此