Sphingosine 1-phosphate promotes the proliferation of olfactory ensheathing cells through YAP signaling and participates in the formation of olfactory nerve layer
Sphingosine 1-phosphate promotes the proliferation of olfactory ensheathing cells through YAP signaling and participates in the formation of olfactory nerve layer
复制标题
1-磷酸鞘氨醇通过YAP信号促进嗅鞘细胞增殖并参与嗅神经层的形成
DOI：
10.1002/glia.23803
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发表时间：
2020-02-14
期刊：
影响因子：
6.2
通讯作者：
Huang, Zhihui
中科院分区：
文献类型：
--
作者：
Bao, Xiaomei;Xu, Xingxing;Huang, Zhihui
嗅鞘细胞（OECs）是嗅上皮和嗅球中具有轴突生长促进特性的独特胶质细胞，覆盖嗅神经的整个长度。嗅鞘细胞的增殖是嗅鞘细胞在发育和移植过程中形成嗅神经层的必要条件。然而，在ONL中OEC增殖调节的分子机制仍然未知。在本研究中，我们研究了1-磷酸鞘氨醇（S1 P）和S1 P受体（S1 PRs）对OEC增殖的作用。逆转录-PCR（RT-PCR）、免疫印迹和免疫组化检测结果表明，S1 PRs在体外和体内的嗅鞘细胞中都有高表达。此外，我们发现S1 P处理促进了由S1 PR 1介导的原代培养的OECs的增殖。从机制上讲，是的相关蛋白（雅普）所需的S1 P诱导的OEC增殖通过RhoA信号。最后，OECs中雅普的条件性敲除减少了ONL中OEC的增殖，这损害了嗅感觉神经元的轴突投射和生长，以及嗅觉功能。综上所述，这些结果揭示了一个以前未被认识到的功能S1 P/RhoA/雅普通路在嗅鞘细胞的增殖，有助于形成ONL和嗅觉感觉神经元的投射，生长和功能在发育过程中。
Olfactory ensheathing cells (OECs) are unique glial cells with axonal growth-promoting properties in the olfactory epithelium and olfactory bulb, covering the entire length of the olfactory nerve. The proliferation of OECs is necessary for the formation of the presumptive olfactory nerve layer (ONL) during development and OECs transplantation. However, the molecular mechanism underlying the regulation of OEC proliferation in the ONL still remains unknown. In the present study, we examined the role of sphingosine 1-phosphate (S1P) and S1P receptors (S1PRs) on OEC proliferation. Initially, reverse transcription-PCR (RT-PCR), western blot and immunostaining revealed that S1PRs were highly expressed in the OECs in vitro and in vivo. Furthermore, we found that S1P treatment promoted the proliferation of primary cultured OECs mediated by S1PR1. Mechanistically, yes-associated protein (YAP) was required for S1P-induced OEC proliferation through RhoA signaling. Finally, conditional knockout of YAP in OECs reduced OEC proliferation in ONL, which impaired the axonal projection and growth of olfactory sensory neurons, and olfactory functions. Taken together, these results reveal a previously unrecognized function of S1P/RhoA/YAP pathway in the proliferation of OECs, contributing to the formation of ONL and the projection, growth, and function of olfactory sensory neurons during development.