Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Genes Dev. 2010 Aug 1;24(15):1614-9. doi: 10.1101/gad.1942810.
Erythrocyte formation occurs throughout life in response to cytokine signaling. We show that microRNA-451 (miR-451) regulates erythropoiesis in vivo. Mice lacking miR-451 display a reduction in hematrocrit, an erythroid differentiation defect, and ineffective erythropoiesis in response to oxidative stress. 14-3-3zeta, an intracellular regulator of cytokine signaling that is repressed by miR-451, is up-regulated in miR-451(-/-) erythroblasts, and inhibition of 14-3-3zeta rescues their differentiation defect. These findings reveal an essential role of 14-3-3zeta as a mediator of the proerythroid differentiation actions of miR-451, and highlight the therapeutic potential of miR-451 inhibitors.
红细胞的生成是终生响应细胞因子信号的结果。我们发现 microRNA-451（miR-451）在体内调节红细胞生成。缺乏 miR-451 的小鼠表现出血细胞比容降低、红系分化缺陷以及对氧化应激的无效红细胞生成。14-3-3zeta 是细胞因子信号的细胞内调节剂，被 miR-451 抑制，在 miR-451(-/-)红细胞中上调，抑制 14-3-3zeta 可挽救其分化缺陷。这些发现揭示了 14-3-3zeta 作为 miR-451 促进原红细胞分化作用的介质的重要作用，并突出了 miR-451 抑制剂的治疗潜力。
