Kondjac ceramide (kier) regulates keratinocyte migration by sema3A-like repulsion mechanism
Kondjac ceramide (kier) regulates keratinocyte migration by sema3A-like repulsion mechanism
复制标题
魔芋神经酰胺 (kier) 通过类 sema3A 排斥机制调节角质形成细胞迁移
DOI：
10.1016/j.bbrep.2018.11.004
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发表时间：
2019
影响因子：
2.7
通讯作者：
Y. Igarashi
中科院分区：
文献类型：
--
作者：
Usuki;N. Tamura;T. Tamura;S. Higashiyama;K. Tanji;S. Mitsutake;A. Inoue;J. Aoki;K. Mukai;Y. Igarashi
以前，我们提出了以下的机制，为kCer神经酰胺（kCer）介导的轴突生长抑制：kCer结合Nrp作为一个Sema 3A激动剂，导致Nrp 1/PlexA复合物的形成和激活的Sema 3A信号通路，诱导磷酸化的CRMP 2和微管解聚。已知Sema 3A/Nrp 1信号通路也在正常人角质形成细胞中表达。为了确定kCer是否可以在人角质形成细胞中发挥作用，就像在神经突中一样，也就是说，如果它可以结合Nrp 1代替Sema 3A，我们研究了kCer对HaCaT细胞迁移活性的影响。使用trans-well chamber测定，我们比较了Sema 3A和kCer对血清来源的细胞迁移活性的影响。kCer显示出Sema 3A样的细胞迁移活性抑制和细胞Cofilin磷酸化的诱导。此外，kCer和Sema 3A抑制组胺（His）增强的未成熟HaCaT细胞的迁移。我们已经证明，kCer不直接与组胺受体H1 R或H4 R相互作用，但我们推测，kCer可能是His信号通路下游的一个信号。
Previously, we proposed the following mechanism for konjac ceramide (kCer)-mediated neurite outgrowth inhibition: kCer binds to Nrp as a Sema3A agonist, resulting in Nrp1/PlexA complex formation and activation of the Sema3A signaling pathway to induce phosphorylation of CRMP2 and microtubule depolymerization. The Sema3A/Nrp1 signaling pathway is known to be also expressed in normal human keratinocytes. To determine whether kCer can function in human keratinocytes as it does in neurites, that is, if it can bind to Nrp1 in place of Sema3A, we studied the effect of kCer on HaCaT cell migration activity. Using a trans-well chamber assay, we compared the effects of Sema3A and kCer on serum-derived cell migration activity. kCer showed Sema3A-like suppression of cell migration activity and induction of cellular Cofilin phosphorylation. In addition, kCer and Sema3A inhibited histamine (His)-enhanced migration of immature HaCaT cells. We have demonstrated that kCer does not interact with histaime receptors H1R or H4R directly, but we speculate that kCer may transduce a signal downstream of the His signaling pathway.