RBM3 promotes neurogenesis in a niche-dependent manner via IMP2-IGF2 signaling pathway after hypoxic-ischemic brain injury
RBM3 promotes neurogenesis in a niche-dependent manner via IMP2-IGF2 signaling pathway after hypoxic-ischemic brain injury
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DOI：
10.1038/s41467-019-11870-x
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发表时间：
2019-09-04
影响因子：
16.6
通讯作者：
Wellmann, Sven
中科院分区：
文献类型：
--
作者：
Zhu, Xinzhou;Yan, Jingyi;Wellmann, Sven
脑缺血（HI）是所有年龄组的急性脑威胁。治疗性低温可改善新生儿的损伤，但其副作用阻止成人常规使用。低温上调一个小的蛋白质亚群，包括RNA结合基序蛋白3（RBM 3），这是在应激条件下的神经保护。在这里，我们展示了RBM 3如何刺激神经元分化和抑制HI诱导的细胞凋亡在两个领域的持续成人神经发生，室管膜下区（SVZ）和颗粒下区（SGZ），同时促进神经干/祖细胞（NSPC）增殖HI损伤后，只有在SGZ。RBM 3与IGF 2 mRNA结合蛋白2（IMP 2）相互作用，提高其表达，从而刺激SGZ而不是SVZ-NSPCs中的IGF 2释放。总之，我们描述了通过新的RBM 3-IMP 2-IGF 2信号通路对成人HI损伤后神经发生的小生境依赖性调节。
Hypoxic ischemia (HI) is an acute brain threat across all age groups. Therapeutic hypothermia ameliorates resulting injury in neonates but its side effects prevent routine use in adults. Hypothermia up-regulates a small protein subset that includes RNA-binding motif protein 3 (RBM3), which is neuroprotective under stressful conditions. Here we show how RBM3 stimulates neuronal differentiation and inhibits HI-induced apoptosis in the two areas of persistent adult neurogenesis, the subventricular zone (SVZ) and the subgranular zone (SGZ), while promoting neural stem/progenitor cell (NSPC) proliferation after HI injury only in the SGZ. RBM3 interacts with IGF2 mRNA binding protein 2 (IMP2), elevates its expression and thereby stimulates IGF2 release in SGZ but not SVZ-NSPCs. In summary, we describe niche-dependent regulation of neurogenesis after adult HI injury via the novel RBM3-IMP2-IGF2 signaling pathway.