蛋白激酶C-ε（PKCε）在敏化初级传入伤害感受器上发挥重要作用，促进机械性过敏。一致地，我们表明PKCε存在于周围神经系统（PNS）的感觉神经元中，参与疼痛发作和慢性化的控制。最近发现PKCε也参与细胞增殖的调控，促进某些癌症类型的有丝分裂和转移入侵。然而，它在PNS主要胶质细胞施旺细胞（SCs）中的作用仍未被调查。我们在大鼠初代SCs培养中采用不同的药物方法，包括PKCε激动剂二环丙基亚油酸（DCP-LA）500 nM，人重组脑源性神经营养因子（BDNF）1 nM以及TrkB受体拮抗剂cyclotraxin B 10 nM。分析了增殖（通过细胞计数），迁移（通过划痕试验和Boyden试验）以及SCs分化和上皮间质转化（EMT）过程的一些标志物（通过qRT-PCR和Western blot）。总体而言，我们发现PKCε在SCs中具有持续表达，可能参与从增殖向分化状态的转变。的确，我们证明PKCε激活调节SCs增殖，增加它们的迁移以及SCs分化的一些标志物（例如糖蛋白P0和转录因子Krox20）的表达。通过一个自分泌机制，BDNF激活TrkB受体，通过PKCε控制SCs增殖。重要的是，PKCε激活可能在SCs中促进了部分EMT过程。PKCε在PNS的神经元和胶质细胞中介导重要作用。特别是，我们提出PKCε在SCs转化中具有新的功能，承担了控制SCs命运和可塑性机制的作用。版权所有 © 2023 Mohamed, Colciago, Montagnani Marelli, Moretti and Magnaghi.

Protein kinase type C-ε (PKCε) plays an important role in the sensitization of primary afferent nociceptors, promoting mechanical hyperalgesia. In accordance, we showed that PKCε is present in sensory neurons of the peripheral nervous system (PNS), participating in the control of pain onset and chronification. Recently, it was found that PKCε is also implicated in the control of cell proliferation, promoting mitogenesis and metastatic invasion in some types of cancer. However, its role in the main glial cell of the PNS, the Schwann cells (SCs), was still not investigated.Rat primary SCs culture were treated with different pharmacologic approaches, including the PKCε agonist dicyclopropyl-linoleic acid (DCP-LA) 500 nM, the human recombinant brain derived neurotrophic factor (BDNF) 1 nM and the TrkB receptor antagonist cyclotraxin B 10 nM. The proliferation (by cell count), the migration (by scratch test and Boyden assay) as well as some markers of SCs differentiation and epithelial-mesenchymal transition (EMT) process (by qRT-PCR and western blot) were analyzed.Overall, we found that PKCε is constitutively expressed in SCs, where it is likely involved in the switch from the proliferative toward the differentiated state. Indeed, we demonstrated that PKCε activation regulates SCs proliferation, increases their migration, and the expression of some markers (e.g., glycoprotein P0 and the transcription factor Krox20) of SCs differentiation. Through an autocrine mechanism, BDNF activates TrkB receptor, and controls SCs proliferation via PKCε. Importantly, PKCε activation likely promoted a partial EMT process in SCs.PKCε mediates relevant actions in the neuronal and glial compartment of the PNS. In particular, we posit a novel function for PKCε in the transformation of SCs, assuming a role in the mechanisms controlling SCs' fate and plasticity.Copyright © 2023 Mohamed, Colciago, Montagnani Marelli, Moretti and Magnaghi.