TGF-β1 enhances phagocytic removal of neuron debris and neuronal survival by olfactory ensheathing cells via integrin/MFG-E8 signaling pathway
TGF-β1 enhances phagocytic removal of neuron debris and neuronal survival by olfactory ensheathing cells via integrin/MFG-E8 signaling pathway
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TGF-β1 通过整合素/MFG-E8 信号通路增强嗅鞘细胞对神经元碎片的吞噬清除和神经元存活
DOI：
10.1016/j.mcn.2017.08.006
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发表时间：
2017-12-01
影响因子：
3.5
通讯作者：
Xu, Haiwei
中科院分区：
文献类型：
--
作者：
Li, Yijian;Zou, Ting;Xu, Haiwei
嗅鞘细胞（OECs）已被证明是中枢神经系统（CNS）损伤和神经退行性疾病细胞治疗的主要候选细胞。在中枢神经系统损伤和神经退行性疾病中，快速清除神经元碎片可促进神经元存活和轴突再生。神经元碎片的吞噬清除已被证明有助于神经元的生长。然而，oec吞噬细胞清除神经元碎片的精确分子和细胞机制尚未被探索。在本研究中，我们发现oec在吞噬清除神经元碎片过程中分泌抗炎细胞因子转化生长因子β 1 （tgf - β 1）。tgf - β 1通过调节整合素/MFG-E8信号通路增强oec的吞噬活性。此外，tgf - β 1使oec向扁平形状移动，细胞面积增加，这也可能参与了oec吞噬活性的增强。此外，oec对神经元碎片的去除影响了神经元的存活和生长。tgf - β 1增强oec对神经元碎片的清除，增加神经元存活。这些结果揭示了tgf - β 1在增强OECs吞噬活性中的作用和机制，这将更新OECs吞噬作用的认识，并改善OECs在中枢神经系统损伤和神经退行性疾病中的治疗应用。
Olfactory ensheathing cells (OECs) have been shown to be a leading candidate in cell therapies for central nervous system (CNS) injuries and neurodegenerative diseases. Rapid clearance of neuron debris can promote neuronal survival and axonal regeneration in CNS injuries and neurodegenerative diseases. The phagocytic removal of neuron debris by OECs has been shown to contribute to neuronal outgrowth. However, the precise molecular and cellular mechanisms of phagocytic removal of neuron debris by OECs have not been explored. In this study, we found that OECs secreted anti-inflammatory cytokine transforming growth factor beta 1 (TGF-beta 1) during the phagocytic removal of neuron debris. TGF-beta 1 enhanced phagocytic activity of OECs through regulating integrin/MFG-E8 signaling pathway. In addition, TGF-beta 1 shifted OECs towards a flattened shape with increased cellular area, which might also be involved in the enhancement of phagocytic activity of OECs. Furthermore, the removal of neuron debris by OECs affected neuronal survival and outgrowth. TGF-beta 1 enhanced the clearance of neuron debris by OECs and increased neuronal survival. These results reveal the role and mechanism of TGF-beta 1 in enhancing the phagocytic activity of OECs, which will update the understanding of phagocytosis of OECs and improve the therapeutic use of OECs in CNS injuries and neurodegenerative diseases.