Tréguer Karine, Heinrich Eva-Marie, Ohtani Kisho, Bonauer Angelika, Dimmeler Stefanie
Institute for Cardiovascular Regeneration, Center of Molecular Medicine, University of Frankfurt, Frankfurt, Germany.
J Vasc Res. 2012;49(5):447-60. doi: 10.1159/000339429. Epub 2012 Jul 11.
MicroRNAs (miRs) are small non-coding RNAs that recently emerged as potent regulators of gene expression. The members of the miR-17-92 cluster have been shown to control endothelial cell functions and neovascularization; however, the regulation and function of the cluster in endothelial cell lineage commitment has not been explored. This project aimed to test the role of the miR-17-92 cluster during endothelial differentiation. We demonstrate that miR-17, miR-18, miR-19 and miR-20 are increased upon the induction of endothelial cell differentiation of murine embryonic stem cells or induced pluripotent stem cells. In contrast, miR-92a and the primary miR-17-92 transcript were downregulated. The inhibition of each individual miR of the cluster by cholesterol-modified antagomirs did not affect endothelial marker gene expression. Moreover, the combination of all antagomirs had no effect. These findings illustrate that although the miR-17-92 cluster regulates vascular integrity and angiogenesis, none of the members has a significant impact on the endothelial differentiation of pluripotent stem cells.
微小RNA（miR）是一类小的非编码RNA，最近被发现是基因表达的强效调节因子。miR-17-92簇的成员已被证明可控制内皮细胞功能和新血管形成；然而，该簇在内皮细胞谱系定向中的调节作用和功能尚未得到研究。本项目旨在测试miR-17-92簇在内皮细胞分化过程中的作用。我们证明，在诱导小鼠胚胎干细胞或诱导多能干细胞向内皮细胞分化时，miR-17、miR-18、miR-19和miR-20的表达会增加。相反，miR-92a和初级miR-17-92转录本的表达则下调。用胆固醇修饰的反义寡核苷酸抑制该簇中的每个单独miR，并不影响内皮标记基因的表达。此外，所有反义寡核苷酸的组合也没有效果。这些发现表明，尽管miR-17-92簇调节血管完整性和血管生成，但该簇的任何成员对多能干细胞的内皮分化均无显著影响。
