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

Qiaochu Sun1, Zhengke Zhi1, Chenglong Wang1

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

Neuroscience Bulletin
|October 1, 2023
PubMed

Insights

A novel peptide, PDYBX1, derived from YBX1, is upregulated in Hirschsprung's disease (HSCR). PDYBX1 counteracts YBX1 downregulation, promoting enteric neural cell migration and proliferation, offering potential HSCR therapeutic strategies.

Area of Science:

  • Molecular biology
  • Developmental biology
  • Gastroenterology

Background:

  • Endogenous peptides regulate cellular processes, but their role in Hirschsprung's disease (HSCR) is unknown.
  • HSCR is a congenital disorder characterized by the absence of enteric ganglia in the distal colon.

Purpose of the Study:

  • To investigate the role of an endogenous peptide derived from YBX1 (PDYBX1) in the pathogenesis of HSCR.
  • To elucidate the molecular mechanism by which PDYBX1 affects enteric neural cell function.

Main Methods:

  • Analysis of YBX1 and PDYBX1 expression in HSCR patient tissues.
  • Transwell and cytoskeleton staining assays to assess cell migration.
  • Immunoprecipitation and immunofluorescence to identify protein interactions.
  • Western blotting to evaluate the ERK1/2 signaling pathway.

Main Results:

  • PDYBX1 expression was upregulated, while its precursor YBX1 was downregulated in aganglionic HSCR colonic tissue.
  • Silencing YBX1 inhibited enteric neural cell migration, an effect partially reversed by PDYBX1 treatment.
  • PDYBX1 binds to ERK2, counteracting YBX1 downregulation-induced ERK1/2 pathway inhibition and promoting cell migration and proliferation.

Conclusions:

  • The endogenous peptide PDYBX1 may mitigate the negative effects of YBX1 downregulation on enteric neural cells in HSCR.
  • PDYBX1 shows potential as a therapeutic agent for HSCR by supporting enteric nervous system development.

Keywords:
Endogenous peptideEnteric neural cellHirschsprung’s diseasePDYBX1YBX1

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