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Dysregulated Transcription Factor TFAP2A After Peripheral Nerve Injury Modulated Schwann Cell Phenotype
Neurochemical Research ( IF 3.7 ) Pub Date : 2019-10-25 , DOI: 10.1007/s11064-019-02898-y
Fuchao Zhang , Xiaokun Gu , Sheng Yi , Hui Xu

Transcription factors regulate the transcriptions and expressions of numerous target genes and direct a variety of physiological and pathological activities. To obtain a better understanding of the involvement of transcription factors during peripheral nerve repair and regeneration, significantly differentially expressed genes coding for transcription factors in rat sciatic nerves after sciatic nerve crush injury were identified. A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identified to be commonly differentially expressed at 1, 4, 7, and 14 days after nerve injury. TFAP2A, a gene encoding transcription factor activating enhancer binding protein 2 alpha, was found to be critical in the regulatory network. PCR validation and immunohistochemistry staining of injured rat sciatic nerves showed that TFAP2A expression was significantly up-regulated in the Schwann cells after nerve injury for at least 2 weeks. Schwann cells transfected with TFAP2A-siRNA exhibited elevated proliferation rate and migration ability, suggesting that TFAP2A suppressed Schwann cell proliferation and migration. Collectively, our study provided a global overview of the dynamic changes of transcription factors after sciatic nerve injury, discovered key transcription factors for the regeneration process, and deepened the understanding of the molecular mechanisms underlying peripheral nerve repair and regeneration.



中文翻译:

周围神经损伤调节雪旺细胞表型后转录因子TFAP2A失调。

转录因子调节许多靶基因的转录和表达,并指导多种生理和病理活动。为了更好地理解转录因子在周围神经修复和再生过程中的参与,鉴定了坐骨神经挤压伤后大鼠坐骨神经中编码转录因子的显着差异表达的基因。总共鉴定出9个转录因子基因,包括GBX2,HIF3A,IRF8,LRRC63,SNAI3,SPIB,TBX21,TFAP2A和ZBTB16,它们在神经损伤后的第1、4、7和14天通常差异表达。发现TFAP2A,一种编码转录因子激活增强子结合蛋白2 alpha的基因,在调节网络中至关重要。受伤大鼠坐骨神经的PCR验证和免疫组织化学染色显示,神经损伤至少2周后,雪旺氏细胞中TFAP2A的表达明显上调。转染了TFAP2A-siRNA的雪旺细胞表现出较高的增殖速率和迁移能力,表明TFAP2A抑制了雪旺细胞的增殖和迁移。总的来说,我们的研究为坐骨神经损伤后转录因子的动态变化提供了一个全球概览,发现了再生过程中的关键转录因子,并加深了对周围神经修复和再生的分子机制的了解。转染了TFAP2A-siRNA的雪旺细胞表现出升高的增殖速率和迁移能力,这表明TFAP2A抑制了雪旺细胞的增殖和迁移。总的来说,我们的研究为坐骨神经损伤后转录因子的动态变化提供了一个全球概览,发现了再生过程中的关键转录因子,并加深了对周围神经修复和再生的分子机制的了解。转染了TFAP2A-siRNA的雪旺细胞表现出较高的增殖速率和迁移能力,表明TFAP2A抑制了雪旺细胞的增殖和迁移。总的来说,我们的研究为坐骨神经损伤后转录因子的动态变化提供了一个全球概览,发现了再生过程中的关键转录因子,并加深了对周围神经修复和再生的分子机制的了解。

更新日期:2019-10-25
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