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c-Fos downregulation positively regulates EphA5 expression in a congenital hypothyroidism rat model

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Abstract

The EphA5 receptor is well established as an axon guidance molecule during neural system development and plays an important role in dendritic spine formation and synaptogenesis. Our previous study has showed that EphA5 is decreased in the developing brain of congenital hypothyroidism (CH) and the EphA5 promoter methylation modification participates in its decrease. c-Fos, a well-kown transcription factor, has been considered in association with brain development. Bioinformatics analysis showed that the EphA5 promoter region contained five putative c-fos binding sites. The chromatin immunoprecipitation (ChIP) assays were used to assess the direct binding of c-fos to the EphA5 promoter. Furthermore, dual-luciferase assays showed that these three c-fos protein binding sites were positive regulatory elements for EphA5 expression in PC12 cells. Moreover, We verified c-fos positively regulation for EphA5 expression in CH model. Q-PCR and Western blot showed that c-fos overexpression could upregulate EphA5 expression in hippocampal neurons of rats with CH. Our results suggest that c-fos positively regulates EphA5 expression in CH rat model.

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Acknowledgements

This study was supported by National Natural Science Youth Fund (81700696), China Postdoctoral Science Foundation (2016M591899), Postdoctoral Science Foundation of Jiangsu Province (1601094C), Nature Science Foundation of Nantong (MS12015002), Youth Key Talent of Medical Foundation of Jiangsu Province (QNRC2016684), 226 high-level talents training project of Nantong (2016).

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Author notes

  1. Honghua Song and Yuqin Zheng are co-first authors and contribute equally to the work.

Authors and Affiliations

  1. Department of Pediatrics, Affiliated Hospital of Nantong University, 20 Xi Si Road, Nantong, 226001, Jiangsu Province, China

    Honghua Song, Yuqin Zheng, Yanyan Ma, Jingyue Yang & Youjia Wu

  2. Department of Pediatrics, Yin Shan Lake Hospital of Wuzhong District, Suzhou, 215100, Jiangsu Province, China

    Fuying Cai

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  1. Honghua Song
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Correspondence to Youjia Wu.

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All the authors report no disclosures relevant to the manuscript. Animal experiments were performed in strict accordance with the Institutional Animal Care guidelines.

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Song, H., Zheng, Y., Cai, F. et al. c-Fos downregulation positively regulates EphA5 expression in a congenital hypothyroidism rat model. J Mol Hist 49, 147–155 (2018). https://doi.org/10.1007/s10735-018-9754-7

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