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Tight Junction Defects in Aganglionic and Ganglionic Colon in Children With Hirschsprung Disease.
Lorena Rincon-Cruz1, Leah Froehle1, Shabnam Abhati2
1Department of General Surgery, Boston Children's Hospital, Boston, Massachusetts.
Laboratory Investigation; a Journal of Technical Methods and Pathology
|December 14, 2025
Summary
Children with Hirschsprung disease (HD) show altered expression of key tight junction proteins, claudin-2, claudin-15, and occludin. These changes in intestinal barrier proteins may contribute to dysfunction and enterocolitis after surgery.
Area of Science:
- Gastroenterology
- Pediatric Surgery
- Molecular Biology
Background:
- Intestinal epithelial barrier dysfunction is implicated in Hirschsprung-associated enterocolitis (HAEC) and intestinal dysfunction in Hirschsprung disease (HD).
- Limited research exists on specific tight junction proteins regulating paracellular permeability in pediatric HD patients.
Purpose of the Study:
- To investigate alterations in colonic epithelial tight junction protein expression in children with HD.
Main Methods:
- Case-control study comparing 29 children with HD and 16 controls.
- Quantitative immunofluorescence microscopy to assess expression of claudins (1, 2, 3, 4, 7, 15), ZO-1, ZO-2, and occludin.
Main Results:
- Reduced expression of claudin-2, claudin-15, and occludin was observed in both ganglionic and aganglionic colon of HD patients compared to controls.
- No significant differences in other assessed tight junction proteins between groups.
Conclusions:
- Decreased claudin-2 and claudin-15 expression may impair hydration and promote fecal stasis, contributing to dysbiosis.
- Reduced occludin expression might increase macromolecular flux and alter epithelial apoptosis sensitivity.
- These protein expression changes may underlie intestinal dysfunction and HAEC pathogenesis post-surgery in HD patients.
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