Wisp2/CCN5 up-regulated in the central nervous system of GM3-only mice facilitates neurite formation in Neuro2a cells via integrin-Akt signaling.
Wisp2/CCN5 up-regulated in the central nervous system of GM3-only mice facilitates neurite formation in Neuro2a cells via integrin-Akt signaling.
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DOI：
10.1016/j.bbrc.2011.06.118
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发表时间：
2011-08
影响因子：
3.1
通讯作者：
Y. Ohkawa;Yuhsuke Ohmi;O. Tajima;Y. Yamauchi;Keiko Furukawa;Kazuro Furukawa
中科院分区：
文献类型：
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作者：
Y. Ohkawa;Yuhsuke Ohmi;O. Tajima;Y. Yamauchi;Keiko Furukawa;Kazuro Furukawa
Wisp2/CCN5属于CCN家族蛋白，参与细胞增殖、血管生成、肿瘤发生和伤口愈合。尽管已有大量关于Wisp2/CCN5在癌症中作用的研究报道，但尚未见Wisp2/CCN5在中枢神经系统中表达和功能的研究报道。在这项研究中，我们关注的是 Wisp2/CCN5，它在仅 GM3 小鼠的神经组织中上调。 Wisp2/CCN5 的过度表达在血清停药后有效增强神经突生长，同时增加 Akt 和 ERK 的磷酸化水平。当细胞与重组 Wisp2/CCN5 蛋白一起培养时，与对照组相比，形成了更多、更长的神经突。因此，我们首次证明 Wisp2/CCN5 促进小鼠神经母细胞瘤细胞系 Neuro2a 中神经突的形成。敲除整合素 β1 后，重组 Wisp2/CCN5 诱导的 Akt 磷酸化受到抑制。此外，Wisp2/CCN5 过表达细胞对 H2O2 诱导的细胞凋亡具有抵抗力。这些结果表明，分泌的 Wisp2/CCN5 通过整合素诱导 Akt 和 ERK 磷酸化，从而促进神经突形成并赋予细胞凋亡抵抗力。因此，仅 GM3 小鼠中 Wisp2/CCN5 的上调应该是保护神经组织免受神经节苷脂缺乏引起的神经变性的反应。
Wisp2/CCN5 belongs to CCN family proteins which are involved in cell proliferation, angiogenesis, tumorigenesis and wound healing. Although a number of studies on the roles of Wisp2/CCN5 in cancers have been reported, no study on the expression and function of Wisp2/CCN5 in the central nervous system has been reported. In this study, we focused on Wisp2/CCN5 that was up-regulated in nervous tissues in GM3-only mice. Over-expression of Wisp2/CCN5 enhanced neurite outgrowth potently after serum withdrawal with increased phosphorylation levels of Akt and ERKs. When cells were cultured with recombinant Wisp2/CCN5 proteins, more and longer neurites were formed than in the controls. Thus, we demonstrated for the first time that Wisp2/CCN5 facilitates neurite formation in a mouse neuroblastoma cell line, Neuro2a. Akt phosphorylation induced by recombinant Wisp2/CCN5 was suppressed after knockdown of integrin β1. Moreover, Wisp2/CCN5-over-expressing cells were resistant to apoptosis induced by H2O2. These results suggested that secreted Wisp2/CCN5 induces Akt and ERK phosphorylation via integrins, and consequently facilitates neurite formation and conferred resistance to apoptosis. Up-regulation of Wisp2/CCN5 in GM3-only mice should be, therefore, a reaction to protect nervous tissues from neurodegeneration caused by ganglioside deficiency.