Hirschsprung’s disease (HSCR)
is characterized by the lack
of ganglion cells in the distal part of the digestive tract. It occurs
due to migration disorders of enteric neural crest cells (ENCCs) from
5 to 12 weeks of embryonic development. More and more studies show
that HSCR is a result of the interaction of multiple genes and the
microenvironments, but its specific pathogenesis has not been fully
elucidated. Studies have confirmed that many substances in the intestinal
microenvironment, such as laminin and β1-integrin, play a vital
regulatory role in cell growth and disease progression. In addition
to these high-molecular-weight proteins, research on endogenous polypeptides
derived from these proteins has been increasing in recent years. However,
it is unclear whether these endogenous peptides have effects on the
migration of ENCCs and thus participate in the occurrence of HSCR.
Previously, our research group found that compared with the normal
intestinal tissue, the expression of AHNAK protein in the stenosed
intestinal tissue of HSCR patients was significantly upregulated,
and overexpression of AHNAK could inhibit cell migration and proliferation.
In this study, endogenous peptides were extracted from the normal
control intestinal tissue and the stenosed HSCR intestinal tissue.
The endogenous polypeptide expression profile was analyzed by liquid
chromatography–mass spectrometry, and multiple peptides derived
from AHNAK protein were found. We selected one of them, “EGPEVDVNLPK”,
for research. Because there is no uniform naming system, this peptide
is temporarily named PDAHNAK (peptide derived from AHNAK). This project
aims to clarify the potential role of PDAHNAK in the development of
HSCR and to further understand its relationship with its precursor
protein AHNAK and how they contribute to the development of HSCR.