The transcription factor Sox11 promotes nerve regeneration through activation of the regeneration-associated gene Sprr1a.
The transcription factor Sox11 promotes nerve regeneration through activation of the regeneration-associated gene Sprr1a.
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DOI：
10.1016/j.expneurol.2011.10.005
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发表时间：
2012-01
影响因子：
5.3
通讯作者：
Albers, Kathryn M.
中科院分区：
文献类型：
--
作者：
Jing, Xiaotang;Wang, Ting;Huang, Shaohua;Glorioso, Joseph C.;Albers, Kathryn M.
增强成年神经元内在生长潜力的因素是损伤后神经元成功修复和再生的关键因素。损伤诱导的转录因子活化在此过程中起着重要作用，因为它们调节再生相关基因的表达。Sox 11是一种发育中表达的转录因子，在成年神经元对损伤的反应中被显著诱导。然而，它在受损神经元中的功能尚不明确。在这里，我们报告的研究，使用单纯疱疹病毒（HSV）载体介导的Sox 11在成人感觉神经元的表达，以评估Sox 11过度表达对神经元再生的影响。培养的小鼠背根神经节（DRG）神经元转染HSV-Sox 11表现出增加的神经突起伸长和分支相对于幼稚和HSV-载体对照处理的神经元。来自在足部皮肤中注射HSV-Sox 11的小鼠的神经元表现出压碎的隐神经的加速再生，如轴突和神经纤维向皮肤的更快再生长、髓鞘厚度增加以及神经和皮肤敏感性的更快恢复所示。通过分析已知再生相关基因的基因表达变化来检查HSV-Sox 11的下游靶点。结合突变和染色质免疫沉淀分析表明，Sox 11加速体内神经再生的能力取决于其再生相关基因小脯氨酸丰富蛋白1a（Sprr 1a）的转录激活。这一发现揭示了Sox 11和Sprr 1a在成人外周神经元再生中的新功能联系。
Factors that enhance the intrinsic growth potential of adult neurons are key players in the successful repair and regeneration of neurons following injury. Injury-induced activation of transcription factors has a central role in this process because they regulate expression of regeneration-associated genes. Sox11 is a developmentally expressed transcription factor that is significantly induced in adult neurons in response to injury. Its function in injured neurons is however undefined. Here, we report studies that use herpes simplex virus (HSV)-vector-mediated expression of Sox11 in adult sensory neurons to assess the effect of Sox11 overexpression on neuron regeneration. Cultured mouse dorsal root ganglia (DRG) neurons transfected with HSV-Sox11 exhibited increased neurite elongation and branching relative to naïve and HSV-vector control treated neurons. Neurons from mice injected in foot skin with HSV-Sox11 exhibited accelerated regeneration of crushed saphenous nerves as indicated by faster regrowth of axons and nerve fibers to the skin, increased myelin thickness and faster return of nerve and skin sensitivity. Downstream targets of HSV-Sox11 were examined by analyzing changes in gene expression of known regeneration-associated genes. This analysis in combination with mutational and chromatin immunoprecipitation assays indicates that the ability of Sox11 to accelerate in vivo nerve regeneration is dependent on its transcriptional activation of the regeneration-associated gene, small proline rich protein 1a (Sprr1a). This finding reveals a new functional linkage between Sox11 and Sprr1a in adult peripheral neuron regeneration.
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影响因子：
2.5
作者：
JENKINS, R;HUNT, SP
通讯作者：
HUNT, SP
DOI：
10.1126/science.1162327
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badis G;Berger MF;Philippakis AA;Talukder S;Gehrke AR;Jaeger SA;Chan ET;Metzler G;Vedenko A;Chen X;Kuznetsov H;Wang CF;Coburn D;Newburger DE;Morris Q;Hughes TR;Bulyk ML
通讯作者：
Bulyk ML
影响因子：
2.5
作者：
Lee, N;Neitzel, KL;MacLennan, AJ
通讯作者：
MacLennan, AJ
影响因子：
5.3
作者：
KARTASOVA, T;VANDEPUTTE, P
通讯作者：
VANDEPUTTE, P
影响因子：
10.5
作者：
Bergsland, Maria;Werme, Martin;Muhr, Jonas
通讯作者：
Muhr, Jonas