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Expression of connexin 26 and connexin 43 is reduced in Hirschsprung's disease
David Coyle1, Brian Doyle2, Justin M Murphy2
1Department of Paediatric Surgery, Temple Street Children's University Hospital, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.
Insights
Connexin (Cx) protein expression, including Cx26 and Cx43, is reduced in the colons of children with Hirschsprung
Area of Science:
- Gastroenterology
- Cell Biology
- Developmental Biology
Background:
- Hirschsprung's disease (HSCR) can cause persistent bowel issues post-surgery.
- Intercellular communication via gap junctions (connexins) is vital for colonic function.
- Understanding connexin expression in HSCR is crucial for addressing motility disorders.
Purpose of the Study:
- To investigate the expression patterns of Cx26, Cx36, and Cx43 in pediatric HSCR colons.
- To compare connexin expression in HSCR tissue with healthy controls.
- To correlate connexin expression with colonic dysmotility in HSCR.
Main Methods:
- Analyzed resected colonic specimens from HSCR patients (n=10) and controls (n=8).
- Utilized double-labeled immunofluorescence and confocal microscopy to assess connexin distribution.
- Quantified protein expression using Western blot analysis.
Main Results:
- Cx36 showed sparse expression in nerve trunks and specific cell types.
- Cx26 and Cx43 were coexpressed with interstitial cells of Cajal (ICCs) in the myenteric plexus.
- Cx26 and Cx43 expression was significantly reduced in aganglionic HSCR colon compared to controls.
Conclusions:
- Reduced Cx26 and Cx43 expression is linked to colonic dysmotility in HSCR.
- Cx26 reduction in ganglionic bowel also contributes to HSCR pathophysiology.
- Gap junction dysfunction may underlie persistent bowel symptoms in HSCR patients.
Background:
Despite having an optimal pull-through operation, some children with Hirschsprung's disease (HSCR) continue to experience persistent bowel symptoms. Coordinated colonic electrical activity depends on intercellular communication between the enteric nerves, interstitial cells of Cajal (ICCs), smooth muscle cells, and fibroblast-like (platelet-derived growth factor receptor-alpha-positive) cells. Gap junctions are low-resistance channels composed of connexin (Cx) proteins which couple cells electrically and chemically. We aimed to evaluate the expression patterns of Cx26, Cx36, and Cx43 in the colon of children with HSCR and in healthy control colon.
Materials And Methods:
Entire resected colonic specimens were collected from children undergoing pull-through surgery for HSCR (n = 10). Colonic controls were collected at colostomy closure in children with imperforate anus (n = 8). Distribution of Cx26, Cx36, and Cx43 was assessed using double-labeled immunofluorescence and confocal microscopy. Protein expression was quantified using Western blot analysis.
Results:
Sparse punctate Cx36 expression was seen in the myenteric plexus in nerve trunks and some platelet-derived growth factor receptor-alpha-positive cell and ICC fibers. Cx26 was similarly distributed, although it was not coexpressed in ICCs. Cx43 was only coexpressed with ICCs in the myenteric plexus. Expression of Cx26 and Cx43 was markedly reduced in the aganglionic colon in HSCR compared to controls, while Cx26 expression was also moderately reduced in the ganglionic bowel in HSCR.
Conclusions:
Reduced expression of Cx26 and Cx43 is implicated in the pathophysiology of colonic dysmotility in the aganglionic bowel as well as, in the case of Cx26, the ganglionic bowel in HSCR.
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