Effect of Spp1 on nerve degeneration and regeneration after rat sciatic nerve injury.

Effect of Spp1 on nerve degeneration and regeneration after rat sciatic nerve injury.
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Spp1对大鼠坐骨神经损伤后神经退变和再生的影响

DOI:
10.1186/s12868-017-0348-1
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发表时间:
2017-03-07
期刊:
影响因子:
2.4
通讯作者:
Yao D
Yao D
中科院分区:
医学4区
文献类型:
--
作者:
Liu X;Sun Y;Li H;Li Y;Li M;Yuan Y;Cui S;Yao D

文献摘要

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研究背景周围神经损伤后的沃勒变性(Wallerian degeneration,WD)与大量上调或下调的基因有关,但这些变化的影响尚不清楚。在我们之前的研究中,我们报告了WD期间差异表达以激活神经变性和再生的一些关键因子。本研究采用大鼠坐骨神经损伤模型,观察了分泌型磷蛋白1(Spp 1)对大鼠坐骨神经损伤后WD的影响。Spp 1在雪旺细胞(SC)中表达的改变导致细胞因子c-Fos、PKCα和磷酸化ERK/ERK的mRNA和蛋白表达水平的改变,并影响SC在体外的凋亡。使用siRNA技术沉默SC中Spp 1的表达降低了体外SC的增殖并促进了其迁移。相反,Spp 1的过表达促进体外SC的增殖并减少其迁移。结论大鼠坐骨神经损伤后,Spp 1通过c-Fos、PKC α和p-ERK/ERK通路参与神经变性和再生,Spp 1在神经变性和再生过程中起重要作用。这些结果为Spp 1在WD神经变性和再生中的作用提供了新的线索。
BackgroundWallerian degeneration (WD) in injured peripheral nerves is associated with a large number of up- or down-regulated genes, but the effects of these changes are poorly understood. In our previous studies, we reported some key factors that are differentially expressed to activate nerve degeneration and regeneration during WD. Here, we determined the effects of secreted phosphoprotein 1 (Spp1) on WD after rat sciatic nerve injury.ResultsSpp1 was upregulated from 6 h to 14 days after sciatic nerve injury. Altered expression of Spp1 in Schwann cells (SC) resulted in altered mRNA and protein expression levels for cytokines, c-Fos, PKCα and phospho-ERK/ERK and affected SC apoptosis in vitro. Silencing of Spp1 expression in SCs using siRNA technology reduced proliferation and promoted migration of SCs in vitro. By contrast, overexpression of Spp1 promoted proliferation and reduced migration in SCs in vitro. Differential expression of Spp1 after sciatic nerve injury in vivo altered the expression of cytokines, c-Fos, PKCα, and the p-ERK/ERK pathway.ConclusionsSpp1 is a key regulatory factor that affects nerve degeneration and regeneration through c-Fos, PKCα and p-ERK/ERK pathways after rat sciatic nerve injury. These results shed new light on the role of Spp1 in nerve degeneration and regeneration during WD.