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Mechanism of Endogenous Peptide PDYBX1 and Precursor Protein YBX1 in Hirschsprung’s Disease

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Abstract

Endogenous peptides, bioactive agents with a small molecular weight and outstanding absorbability, regulate various cellular processes and diseases. However, their role in the occurrence of Hirschsprung’s disease (HSCR) remains unclear. Here, we found that the expression of an endogenous peptide derived from YBX1 (termed PDYBX1 in this study) was upregulated in the aganglionic colonic tissue of HSCR patients, whereas its precursor protein YBX1 was downregulated. As shown by Transwell and cytoskeleton staining assays, silencing YBX1 inhibited the migration of enteric neural cells, and this effect was partially reversed after treatment with PDYBX1. Moreover, immunoprecipitation and immunofluorescence revealed that ERK2 bound to YBX1 and PDYBX1. Downregulation of YBX1 blocked the ERK1/2 pathway, but upregulation of PDYBX1 counteracted this effect by binding to ERK2, thereby promoting cell migration and proliferation. Taken together, the endogenous peptide PDYBX1 may partially alleviate the inhibition of the ERK1/2 pathway caused by the downregulation of its precursor protein YBX1 to antagonize the impairment of enteric neural cells. PDYBX1 may be exploited to design a novel potential therapeutic agent for HSCR.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (82001590, 81801496, and 82270540).

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  1. Qiaochu Sun and Zhengke Zhi contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Surgery, Children’s Hospital of Nanjing Medical University, Nanjing, 210008, China

    Qiaochu Sun, Zhengke Zhi, Chenglong Wang, Chunxia Du, Jie Tang, Hongxing Li & Weibing Tang

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  1. Qiaochu Sun
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  2. Zhengke Zhi
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Correspondence to Hongxing Li or Weibing Tang.

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Sun, Q., Zhi, Z., Wang, C. et al. Mechanism of Endogenous Peptide PDYBX1 and Precursor Protein YBX1 in Hirschsprung’s Disease. Neurosci. Bull. (2023). https://doi.org/10.1007/s12264-023-01132-8

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