Department of Nephrology, LUMC, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
Cardiovasc Res. 2011 Dec 1;92(3):449-55. doi: 10.1093/cvr/cvr227. Epub 2011 Aug 19.
MicroRNA-126 (miR-126), which is enriched in endothelial cells, plays a role in angiogenesis. Based on the seed sequence, miR-126 can also be predicted to regulate vasculogenesis by modulating the endothelial expression of stromal cell-derived factor-1 (SDF-1).
Using miR-reporter constructs, we first validated that miR-126 inhibits SDF-1 expression in endothelial cells in vitro. Next, we investigated the potential relevance of this observation with respect to the mobilization of progenitor cells. For this, we studied the migration of human CD34+ progenitor cells towards chemotactic factors present in endothelial cell-conditioned medium. Antagomir-induced silencing of miR-126 elevated SDF-1 expression by human umbilical vein endothelial cells and enhanced migration of the CD34+ cells. In a murine model of hind limb ischaemia, a striking increase in the number of circulating Sca-1(+)/Lin(-) progenitor cells in antagomir-126-treated mice was observed when compared with scramblemir-treated controls. Immunohistochemical staining of capillaries in the post-ischaemic gastrocnemius muscle of miR-126-silenced mice revealed elevated SDF-1 expressing CD31-positive capillaries, whereas a mobilizing effect of miR-126 inhibition was not detected in healthy control animals.
miR-126 can regulate the expression of SDF-1 in endothelial cells. In the context of an ischaemic event, systemic silencing of miR-126 leads to the mobilization of Sca-1(+)/Lin(-) progenitor cells into the peripheral circulation, potentially in response to elevated SDF-1 expression by endothelial cells present in the ischaemic tissue.
富含在内皮细胞中的 microRNA-126（miR-126）在血管生成中发挥作用。基于种子序列，miR-126 也可以通过调节基质细胞衍生因子-1（SDF-1）的内皮表达来调节血管发生。
我们首先使用 miR-报告基因构建体验证了 miR-126 在体外抑制内皮细胞中 SDF-1 的表达。接下来，我们研究了这一观察结果与祖细胞动员的潜在相关性。为此，我们研究了人类 CD34+祖细胞向内皮细胞条件培养基中存在的趋化因子的迁移。抗 miR-126 诱导的沉默增加了人脐静脉内皮细胞中 SDF-1 的表达，并增强了 CD34+细胞的迁移。在小鼠后肢缺血模型中，与 scramble 对照相比，抗 miR-126 处理的小鼠中循环 Sca-1(+)/Lin(-)祖细胞的数量显著增加。在 miR-126 沉默的小鼠缺血后比目鱼肌中的毛细血管免疫组织化学染色显示，SDF-1 表达的 CD31 阳性毛细血管增加，而在健康对照动物中未检测到 miR-126 抑制的动员作用。
miR-126 可以调节内皮细胞中 SDF-1 的表达。在缺血事件的背景下，系统性沉默 miR-126 导致 Sca-1(+)/Lin(-)祖细胞动员到外周循环中，可能是对缺血组织中内皮细胞中 SDF-1 表达升高的反应。
