Dysregulated Transcription Factor TFAP2A After Peripheral Nerve Injury Modulated Schwann Cell Phenotype
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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.
KeywordsTranscription factor TFAP2A Peripheral nerve injury Schwann cells Proliferation Migration
Conceived and designed the experiments: SY HX. Performed the experiments: FZ XG. Analyzed the data: FZ XG SY. Contributed reagents/materials/analysis tools: SY. Wrote the manuscript: SY HX.
This work was supported by the National Natural Science Foundation of China , and the Priority Academic Program Development of Jiangsu Higher Education Institutions of China [PAPD].
Compliance with Ethical Standards
Ethics Approval and Consent to Participate
All the experimental procedures involving animals were conducted in accordance with Institutional Animal Care guidelines of Nantong University and approved ethically by the Administration Committee of Experimental Animals, Jiangsu, China.
- 14.Chen ZL, Yu WM, Strickland S (2007) Peripheral regeneration. Annu Rev Neurosci 30:209–233. https://doi.org/10.1146/annurev.neuro.30.051606.094337 CrossRefGoogle Scholar
- 20.Oliveros JC (2007) VENNY. An interactive tool for comparing lists with Venn DiagramsGoogle Scholar
- 25.Li Q, Dashwood RH (2004) Activator protein 2alpha associates with adenomatous polyposis coli/beta-catenin and Inhibits beta-catenin/T-cell factor transcriptional activity in colorectal cancer cells. J Biol Chem 279(44):45669–45675. https://doi.org/10.1074/jbc.M405025200 CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Braganca J, Swingler T, Marques FI, Jones T, Eloranta JJ, Hurst HC, Shioda T, Bhattacharya S (2002) Human CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) 4, a new member of the CITED family, functions as a co-activator for transcription factor AP-2. J Biol Chem 277(10):8559–8565. https://doi.org/10.1074/jbc.M110850200 CrossRefPubMedGoogle Scholar
- 35.Ding X, Yang Z, Zhou F, Wang F, Li X, Chen C, Li X, Hu X, Xiang S, Zhang J (2013) Transcription factor AP-2alpha regulates acute myeloid leukemia cell proliferation by influencing Hoxa gene expression. Int J Biochem Cell Biol 45(8):1647–1656. https://doi.org/10.1016/j.biocel.2013.04.024 CrossRefPubMedGoogle Scholar