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首页> 外文期刊>The Journal of biological chemistry >The active component of ginseng, ginsenoside Rb1, improves erythropoiesis in models of Diamond–Blackfan anemia by targeting Nemo-like kinase
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The active component of ginseng, ginsenoside Rb1, improves erythropoiesis in models of Diamond–Blackfan anemia by targeting Nemo-like kinase

机译：人参，人参皂苷Rb1的活性成分通过靶向NemO样激酶改善了金刚石 - 黑葡萄酒贫血模型中的促红细胞产物

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摘要

Nemo-like kinase (NLK) is a member of the mitogen-activated protein kinase family of kinases and shares a highly conserved kinase domain with other mitogen-activated protein kinase family members. The activation of NLK contributes to the pathogenesis of Diamond–Blackfan anemia (DBA), reducing c-myb expression and mechanistic target of rapamycin activity, and is therefore a potential therapeutic target. Unlike other anemias, the hematopoietic effects of DBA are largely restricted to the erythroid lineage. Mutations in ribosomal genes induce ribosomal insufficiency and reduced protein translation, dramatically impacting early erythropoiesis in the bone marrow of patients with DBA. We sought to identify compounds that suppress NLK and increases erythropoiesis in ribosomal insufficiency. We report that the active component of ginseng, ginsenoside Rb1, suppresses NLK expression and improves erythropoiesis in in vitro models of DBA. Ginsenoside Rb1–mediated suppression of NLK occurs through the upregulation of miR-208, which binds to the 3′-UTR of NLK mRNA and targets it for degradation. We also compare ginsenoside Rb1–mediated upregulation of miR-208 with metformin-mediated upregulation of miR-26. We conclude that targeting NLK expression through miRNA binding of the unique 3′-UTR is a viable alternative to the challenges of developing small-molecule inhibitors to target the highly conserved kinase domain of this specific kinase.
机译：类似NemO样激酶（NLK）是丝裂原激活的蛋白激酶系酶的成员，并与其他丝裂原激活的蛋白激酶系成员分享高度保守的激酶结构域。 NLK的活化有助于金刚石 - 黑葡萄酒贫血（DBA）的发病机制，降低雷帕霉素活性的C-MYB表达和机械靶，因此是潜在的治疗靶标。与其他耳子不同，DBA的造血作用主要限于红细胞谱系。核糖体基因的突变诱导核糖体不足和蛋白质翻译降低，显着影响DBA患者骨髓中的早期促红细胞病毒。我们试图鉴定抑制NLK的化合物，并增加核糖体功能不全的红细胞产物。我们认为人参，人参皂苷RB1，抑制NLK表达并改善DBA体外模型中的红细胞生成。人参皂甙RB1介导的NLK抑制通过MIR-208的上调，其结合NLK mRNA的3'-UTR并靶向降解。我们还将人参皂甙RB1介导的MIR-208介导的MIR-208介导的MIR-26上调的上调。我们得出结论，通过独特的3'-UTR的miRNA结合靶向NLK表达是一种可行的替代挑战，所述挑战小分子抑制剂靶向该特异性激酶的高度保守的激酶结构域。

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