Zhang Weidong, Zhu Xudong, Liu Yang, Chen Minhao, Yan Shixian, Mao Xingxing, Liu Zhongbing, Wu Weijie, Chen Chen, Xu Xinbao, Wang Youhua
Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
J Mol Neurosci. 2015 Sep;57(1):38-47. doi: 10.1007/s12031-015-0575-9. Epub 2015 May 10.
Nur77, together with Nurr1 and NOR-1, constitutes the NR4A subgroup of orphan nuclear receptors and plays critical roles in cell proliferation, differentiation, migration, and apoptosis. Among them, Nur77 is universally well known to contribute to neurite outgrowth. However, information regarding its regulation and possible function in the peripheral nervous system is still limited. In this study, we performed a sciatic nerve injury model in adult rats and detected an increased expression of Nur77 in the sciatic nerve, which was similar to the expression of Oct-6. Immunofluorescence indicated that Nur77 was located in both axons and Schwann cells. In vitro, we observed enhanced expression of Nur77 during the process of both basic fibroblast growth factor (bFGF)-induced Schwann cells differentiation and nerve growth factor (NGF)-induced PC12 cell neurite outgrowth. In vitro and in vivo experiments indicated that inhibiting the function of Nur77 by specific short hairpin RNA could depress Schwann cells myelinization and axons regeneration. Collectively, all these results suggested that upregulation of Nur77 might be involved in Schwann cells differentiation and neurite elongation following sciatic nerve crush.
Nur77与Nurr1和NOR-1共同构成孤儿核受体的NR4A亚组，在细胞增殖、分化、迁移和凋亡中发挥关键作用。其中，Nur77促进神经突生长这一点广为人知。然而，关于其在周围神经系统中的调控及可能功能的信息仍然有限。在本研究中，我们在成年大鼠中建立了坐骨神经损伤模型，并检测到坐骨神经中Nur77的表达增加，这与Oct-6的表达情况相似。免疫荧光显示Nur77位于轴突和雪旺细胞中。在体外，我们观察到在碱性成纤维细胞生长因子（bFGF）诱导雪旺细胞分化以及神经生长因子（NGF）诱导PC12细胞神经突生长的过程中，Nur77的表达均增强。体外和体内实验表明，通过特异性短发夹RNA抑制Nur77的功能可抑制雪旺细胞髓鞘化和轴突再生。总的来说，所有这些结果表明，Nur77的上调可能参与坐骨神经挤压后雪旺细胞的分化和神经突伸长。
