Two Pathways Regulate Differential Expression of nAChRs Between the Orbicularis Oris and Gastrocnemius
Two Pathways Regulate Differential Expression of nAChRs Between the Orbicularis Oris and Gastrocnemius
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两种途径调节口轮匝肌和腓肠肌之间 nAChR 的差异表达
DOI：
10.1016/j.jss.2019.04.056
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发表时间：
2019-11-01
影响因子：
2.2
通讯作者：
Li, Shitong
中科院分区：
文献类型：
--
作者：
Wu, Shuang;Huang, Yong;Li, Shitong
背景资料：我们先前证明了面神经支配的口轮匝肌和体神经支配的腓肠肌中烟碱乙酰胆碱受体（nAChRs）的差异表达，这有助于对肌肉松弛剂的不同敏感性。此外，口轮匝肌表现出较低的敏感性，肌肉松弛剂面神经损伤后，这也与nAChRs的上调。在这里，我们探讨了不同的表达模式的调控机制。由于聚集蛋白/Lrp 4/MuSK/rapsyn和神经调节蛋白1/ErbB信号通路对于维持nAChRs的表达是必不可少的，我们检查了这两种信号通路在正常或受损面神经支配的腓肠肌和口轮匝肌中的活性。通过免疫荧光实现了这两种信号通路的定量分析，免疫沉淀法检测面神经损伤后腓肠肌和口轮匝肌磷酸化MuSK的表达。ErbB和磷酸化MuSK在口轮匝肌的表达高于腓肠肌（P < 0.05）。agrin/Lrp 4/MuSK/rapsyn的表达差异无统计学意义。面神经损伤后，聚集蛋白的水平和磷酸化的MuSK的百分比显着下降，虽然MuSK，rapsyn，和neuregulin 1/ErbB.Conclusions的表达水平高度上调：neuregulin 1/ErbB信号通路的差异表达可能占不同的表达模式的nAChRs在口轮匝肌和腓肠肌的神经肌肉接头。MuSK和rapsyn的过表达可能有助于面神经损伤后nAChRs的上调。(C)2019爱思唯尔公司All rights reserved.
Background: We previously demonstrated differential expression of nicotinic acetylcholine receptors (nAChRs) in the facial nerve-innervated orbicularis oris and somatic nerveinnervated gastrocnemius, which contribute to different sensitivities to muscle relaxants. Furthermore, the orbicularis oris exhibits less sensitivity to muscle relaxants after facial nerve injury, which is also related to upregulation of nAChRs. Here, we explored the regulatory mechanism for the different expression patterns. Because the agrin/Lrp4/MuSK/rapsyn and neuregulin1/ErbB signaling pathways are indispensable for maintaining the expression of nAChRs, we examined the activity of these two signaling pathways in gastrocnemius and orbicularis oris innervated by normal or injured facial nerves.Materials and methods: A quantitative analysis of these two signaling pathways was realized by immunofluorescence, and immunoprecipitation was applied to detect the level of phosphorylated MuSK in the gastrocnemius and orbicularis oris innervated by normal or injured facial nerves in adult rats.Results: ErbB and the phosphorylated MuSK were expressed more in orbicularis oris than in gastrocnemius (P < 0.05). No significant difference was found in the expression of agrin/Lrp4/MuSK/rapsyn. After facial nerve injury, the level of agrin and the percentage of phosphorylated MuSK decreased significantly, although the expression levels of MuSK, rapsyn, and neuregulin1/ErbB were highly upregulated.Conclusions: Differential expression of the neuregulin1/ErbB signaling pathway may account for the different expression patterns of nAChRs at the neuromuscular junctions of the orbicularis oris and gastrocnemius. Overexpression of MuSK and rapsyn may contribute to upregulation of nAChRs after facial nerve injury. (C) 2019 Elsevier Inc. All rights reserved.