Dysregulated Transcription Factor TFAP2A After Peripheral Nerve Injury Modulated Schwann Cell Phenotype

Dysregulated Transcription Factor TFAP2A After Peripheral Nerve Injury Modulated Schwann Cell Phenotype
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周围神经损伤后转录因子 TFAP2A 失调调节雪旺细胞表型

DOI:
10.1007/s11064-019-02898-y
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发表时间:
2019-10
影响因子:
4.4
通讯作者:
Xu Hui
Xu Hui
中科院分区:
医学3区
文献类型:
--
作者:
Zhang Fuchao;Gu Xiaokun;Yi Sheng;Xu Hui

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转录因子调控着许多靶基因的转录和表达,指导着多种生理和病理活动。为了更好地了解周围神经修复和再生过程中转录因子的参与,在大鼠坐骨神经挤压伤后的坐骨神经中鉴定了编码转录因子的显著差异表达基因。在神经损伤后1、4、7和14天,总共鉴定了9个转录因子基因,包括GBX 2、HIF 3A、IRF 8、LRRC 63、SNAI 3、SPIB、TBX 21、TFAP 2A和ZBTB 16,其通常差异表达。TFAP 2A是一种编码转录因子激活增强子结合蛋白2 α的基因,被发现在调控网络中至关重要。PCR验证和免疫组化染色显示,TFAP 2A表达显着上调后,神经损伤至少2周的雪旺细胞。转染TFAP 2A-siRNA的雪旺细胞增殖率和迁移能力明显升高,提示TFAP 2A抑制雪旺细胞增殖和迁移。总之,我们的研究提供了坐骨神经损伤后转录因子的动态变化的全局性概述,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理解。
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.
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