Transient lysosomal activation is essential for p75 nerve growth factor receptor expression in myelinated Schwann cells during Wallerian degeneration.
Transient lysosomal activation is essential for p75 nerve growth factor receptor expression in myelinated Schwann cells during Wallerian degeneration.
复制标题
在沃勒式变性过程中，瞬时溶酶体激活对于髓鞘的Schwann细胞中的p75神经生长因子受体表达至关重要。
DOI：
10.5115/acb.2011.44.1.41
复制
发表时间：
2011-03
影响因子：
1.1
通讯作者：
Park HT
中科院分区：
文献类型：
--
作者：
Jung J;Cai W;Jang SY;Shin YK;Suh DJ;Kim JK;Park HT
周围神经系统中的有髓雪旺细胞表达 p75 神经生长因子受体 (p75NGFR)，这是华勒变性过程中雪旺细胞去分化的结果。 p75NGFR 与再生神经的髓鞘再生有关。尽管许多研究已经表明雪旺细胞去分化的多种机制，但在分化的雪旺细胞中导致 p75NGFR 重新表达的分子机制在很大程度上尚不清楚。在本研究中，我们发现神经损伤后雪旺细胞中的溶酶体被短暂激活，并且在离体华勒变性模型中，氯喹或溶酶体酸化抑制剂抑制溶酶体激活可阻止 p75NGFR 在 mRNA 转录水平上的表达。溶酶体酸化抑制剂抑制脱髓鞘，但不抑制轴突变性，从而表明溶酶体介导的脱髓鞘可能是诱导 p75NGFR 表达的重要信号。肿瘤坏死因子-α (TNF-α) 被认为参与调节雪旺细胞中 p75NGFR 的表达。在这项研究中，我们发现体内去除 TNF-α 并没有显着抑制溶酶体和 p75NGFR 的诱导。因此，这些发现表明溶酶体激活与沃勒变性期间脱髓鞘雪旺细胞中 p75NGFR 的诱导密切相关。
Myelinated Schwann cells in the peripheral nervous system express the p75 nerve growth factor receptor (p75NGFR) as a consequence of Schwann cell dedifferentiation during Wallerian degeneration. p75NGFR has been implicated in the remyelination of regenerating nerves. Although many studies have shown various mechanisms underlying Schwann cell dedifferentiation, the molecular mechanism contributing to the re-expression of p75NGFR in differentiated Schwann cells is largely unknown. In the present study, we found that lysosomes were transiently activated in Schwann cells after nerve injury and that the inhibition of lysosomal activation by chloroquine or lysosomal acidification inhibitors prevented p75NGFR expression at the mRNA transcriptional level in an ex vivo Wallerian degeneration model. Lysosomal acidification inhibitors suppressed demyelination, but not axonal degeneration, thereby suggesting that demyelination mediated by lysosomes may be an important signal for inducing p75NGFR expression. Tumor necrosis factor-α (TNF-α) has been suggested to be involved in regulating p75NGFR expression in Schwann cells. In this study, we found that removing TNF-α in vivo did not significantly suppress the induction of both lysosomes and p75NGFR. Thus, these findings suggest that lysosomal activation is tightly correlated with the induction of p75NGFR in demyelinating Schwann cells during Wallerian degeneration.