Neuroscience ( IF 3.3 ) Pub Date : 2020-03-18 , DOI: 10.1016/j.neuroscience.2020.03.007 Jiannan Li 1 , Zhan Zhang 1 , Jiangbo Wang 1 , Shuang Du 1 , Dengbing Yao 2 , Rangjuan Cao 1 , Shusen Cui 1
Wallerian degeneration (WD) and axon regeneration generally take place following peripheral nerve injury (PNI). Schwann cells (SCs) and macrophages play major role in WD. SCs, acting as repair cells and primary signal mediators, dedifferentiate and proliferate to remove the debris, form Büngner’s bands and secrete trophic factors during these processes. However, the underlying mechanisms remain poorly understood. Here, we found that protein kinase Cα (PKCα), a serine/threonine kinase, expressed in SCs was significantly up-regulated after PNI. Activating PKCα with phorbol 12-myristate 13-acetate (PMA), a phorbol ester binds and activates PKCα) promoted SCs proliferation and migration. While, silence of PKCα by siRNAs inhibited these processes. PD184352, an inhibitor of MEK1, reversed the effect induced by PMA on SCs. Mechanism studies revealed that PKCα functioned through activating the ERK signaling pathway. Furthermore, PKCα also exhibited a neuroprotective role by upregulating the expression of neurotrophic factors in SCs. To sum up, this study offers novel insights for clarifying our understanding of the involvement of PKCα in the mechanism of peripheral nerve degeneration as well as regeneration.
中文翻译:
蛋白激酶Cα通过激活ERK信号通路促进雪旺细胞的增殖和迁移。
Wallerian变性(WD)和轴突再生通常发生在周围神经损伤(PNI)之后。雪旺氏细胞(SCs)和巨噬细胞在WD中起主要作用。作为修复细胞和主要信号介体的SC脱分化并增殖以清除碎屑,形成邦格氏带并在这些过程中分泌营养因子。但是,基本机制仍然知之甚少。在这里,我们发现PNI后在SC中表达的蛋白激酶Cα(PKCα)是一种丝氨酸/苏氨酸激酶,其表达明显上调。用佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)激活PKCα,佛波醇酯结合并激活PKCα)促进了SCs的增殖和迁移。同时,siRNA沉默PKCα抑制了这些过程。MEK1抑制剂PD184352逆转了PMA对SC诱导的作用。机制研究表明,PKCα通过激活ERK信号通路起作用。此外,PKCα还通过上调SC中神经营养因子的表达而发挥神经保护作用。综上所述,本研究为阐明我们对PKCα参与周围神经变性及再生机制的理解提供了新颖的见解。