Protein Kinase Ca Promotes Proliferation and Migration of Schwann Cells by Activating ERK Signaling Pathway
Protein Kinase Ca Promotes Proliferation and Migration of Schwann Cells by Activating ERK Signaling Pathway
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蛋白激酶Ca通过激活ERK信号通路促进雪旺细胞增殖和迁移
DOI：
10.1016/j.neuroscience.2020.03.007
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发表时间：
2020-05-01
期刊：
影响因子：
3.3
通讯作者：
Cui, Shusen
中科院分区：
文献类型：
--
作者：
Li, Jiannan;Zhang, Zhan;Cui, Shusen
沃勒变性（WD）和轴突再生通常发生在周围神经损伤（PNI）之后。雪旺细胞和巨噬细胞在WD中起主要作用。干细胞作为修复细胞和主要信号介质，在这些过程中去分化和增殖以去除碎片，形成Bungner带并分泌营养因子。然而，对潜在的机制仍然知之甚少。在这里，我们发现蛋白激酶C α（PKC α），一种丝氨酸苏氨酸激酶，在SC中表达，在PNI后显著上调。用佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）激活PKC α，佛波酯结合并激活PKC α）促进SC增殖和迁移。而siRNA沉默PKC α则抑制了这些过程。MEK 1抑制剂PD 184352可逆转PMA对SC的诱导作用。机制研究表明PKC α通过激活ERK信号通路发挥作用。此外，PKC α还通过上调SC中神经营养因子的表达而表现出神经保护作用。综上所述，本研究为阐明我们对PKC α参与周围神经变性和再生机制的理解提供了新的见解。(C)2020年IBRO。由爱思唯尔有限公司出版。保留所有权利。
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 Bungner's bands and secrete trophic factors during these processes. However, the underlying mechanisms remain poorly understood. Here, we found that protein kinase C alpha (PKC alpha), a serineithreonine kinase, expressed in SCs was significantly up-regulated after PNI. Activating PKC alpha with phorbol 12-myristate 13-acetate (PMA), a phorbol ester binds and activates PKC alpha) promoted SCs proliferation and migration. While, silence of PKC alpha by siRNAs inhibited these processes. PD184352, an inhibitor of MEK1, reversed the effect induced by PMA on SCs. Mechanism studies revealed that PKC alpha functioned through activating the ERK signaling pathway. Furthermore, PKC alpha 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 PKC alpha in the mechanism of peripheral nerve degeneration as well as regeneration. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.