Secretome analysis of nerve repair mediating Schwann cells reveals Smad-dependent trophism
Secretome analysis of nerve repair mediating Schwann cells reveals Smad-dependent trophism
复制标题
DOI：
10.1096/fj.201801799r
复制
发表时间：
2019-04-01
期刊：
影响因子：
4.8
通讯作者：
Kuery, Patrick
中科院分区：
文献类型：
--
作者：
Schira, Jessica;Heinen, Andre;Kuery, Patrick
雪旺细胞通过适应一种被称为修复介导雪旺细胞的再生表型来促进神经再生。髓鞘蛋白的下调、髓鞘的清除、邦纳带的形成和营养因子的分泌是这种细胞的特征。我们先前已经证明，鞘氨醇-1-磷酸受体激动剂Fingolimod/FTY720P通过激活去分化标志物和伴随的营养因子的释放促进这种特殊的雪旺细胞表型的产生，从而促进背根神经节神经元的轴突生长。尽管FTY720P与生物医学相关，但对相应的雪旺细胞分泌组的详细表征尚不清楚，FTY720P在促进轴突生长方面的影响也不明确。在这里，我们应用了一种无标记的定量质谱学方法来表征原代新生和成年大鼠雪旺细胞对FTY720P的反应产生的分泌体。我们发现在新生儿和成人雪旺细胞之间有很大比例的高度重叠的分泌蛋白，这可能与发育、轴突生长和再生等生物过程有关。此外，FTY720P处理的雪旺细胞释放Smad信号下游的蛋白质，支持轴突生长。因此，我们的结果揭示了参与神经胶质细胞介导的周围神经系统修复的营养因子网络。
Schwann cells promote nerve regeneration by adaptation of a regenerative phenotype referred to as repair mediating Schwann cell. Down-regulation of myelin proteins, myelin clearance, formation of Bungner's bands, and secretion of trophic factors characterize this cell type. We have previously shown that the sphingosine-1-phosphate receptor agonist Fingolimod/FTY720P promotes the generation of this particular Schwann cell phenotype by activation of dedifferentiation markers and concomitant release of trophic factors resulting in enhanced neurite growth of dorsal root ganglion neurons. Despite its biomedical relevance, a detailed characterization of the corresponding Schwann cell secretome is lacking, and the impact of FTY720P on enhancing neurite growth is not defined. Here, we applied a label-free quantitative mass spectrometry approach to characterize the secretomes derived from primary neonatal and adult rat Schwann cells in response to FTY720P. We identified a large proportion of secreted proteins with a high overlap between the neonatal and adult Schwann cells, which can be associated with biologic processes such as development, axon growth, and regeneration. Moreover, FTY720P-treated Schwann cells release proteins downstream of Smad signaling known to support neurite growth. Our results therefore uncover a network of trophic factors involved in glial-mediated repair of the peripheral nervous system.