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Altered expression of caveolin-1 in the colon of patients with Hirschsprung’s disease

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Abstract

Background/purpose

The pathogenesis of Hirschsprung’s disease-associated enterocolitis (HAEC) is unclear. Caveolin-1 (Cav-1) regulates the functions of different nitric oxide synthase (NOS) isoforms, which play critical roles in inflammation and intestinal epithelial barrier function. We designed this study to investigate the hypothesis that Cav-1 expression is altered in the bowel of patients with Hirschsprung’s disease (HSCR).

Methods

HSCR tissue specimens (n = 10) were collected at the time of pull-through surgery and control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 10). qRT-PCR analysis was undertaken to quantify Cav-1 gene expression, and Western blot analysis was undertaken to determine Cav-1 protein quantification. Immunolabelling of Cav-1 proteins was visualized using confocal microscopy.

Results

qRT-PCR and Western blot analysis revealed that Cav-1 was significantly downregulated in the aganglionic and ganglionic colon of patients with HSCR compared to controls (p < 0.01). Confocal microscopy revealed a markedly decreased expression of Cav-1 in colonic epithelium of aganglionic and ganglionic bowel of patients with HSCR compared to controls.

Conclusion

To our knowledge, this is the first report of significantly decreased Cav-1 expression in patients with HSCR. Decreased expression of Cav-1 in the bowel of HSCR may increase susceptibility to HAEC in HSCR.

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Authors and Affiliations

  1. National Children’s Research Centre, Our Lady’s Children’s Hospital, Dublin, Ireland

    Hiroki Nakamura, Anne Marie O’Donnell, Christian Tomuschat, David Coyle & Prem Puri

  2. School of Medicine and Medical Science and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland

    Prem Puri

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  1. Hiroki Nakamura
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  2. Anne Marie O’Donnell
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  3. Christian Tomuschat
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  4. David Coyle
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  5. Prem Puri
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Correspondence to Prem Puri.

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Nakamura, H., O’Donnell, A.M., Tomuschat, C. et al. Altered expression of caveolin-1 in the colon of patients with Hirschsprung’s disease. Pediatr Surg Int 35, 929–934 (2019). https://doi.org/10.1007/s00383-019-04505-1

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