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Pediatric Surgery International

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01.11.2018 | Original Article

Abnormal Scn1b and Fxyd1 gene expression in the pulled-through ganglionic colon may influence functional outcome in patients with Hirschsprung’s disease

verfasst von: Anne Marie O’Donnell, Hiroki Nakamura, Christian Tomuschat, Naoum Fares Marayati, Prem Puri

Erschienen in: Pediatric Surgery International | Ausgabe 1/2019

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Abstract

Purpose

Smooth muscle cells are electrically coupled to ICC and PDGFRα⁺ cells, to regulate smooth muscle contraction. Recent studies have reported that the voltage-gated sodium channel type 1β (Scn1b), and the chloride channel subunit, Fxyd1, are highly expressed by both ICC and PDGFRα⁺ cells in the mouse colon. We designed this study to investigate the expression of the Scn1b and Fxyd1 genes in the normal human colon and in HSCR.

Methods

HSCR tissue specimens (n = 6) were collected at the time of pull-through surgery, while control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 6). qRT-PCR analysis was undertaken to quantify Scn1b and Fxyd1 gene expression, and immunolabelling of Scn1b and Fxyd1 proteins were visualized using confocal microscopy.

Results

qRT-PCR analysis revealed significant downregulation of Scn1b and Fxyd1 genes in both aganglionic and ganglionic HSCR specimens compared to controls (p < 0.05). Confocal microscopy revealed a reduction in Scn1b and Fxyd1 protein expression in both aganglionic and ganglionic HSCR colon compared to controls.

Conclusion

Scn1b and Fxyd1 expression was significantly downregulated in HSCR colon. These results add to mounting evidence suggesting that the pulled-through ganglionic segment of bowel in these patients is abnormal, despite the presence of ganglion cells.

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Titel: Abnormal Scn1b and Fxyd1 gene expression in the pulled-through ganglionic colon may influence functional outcome in patients with Hirschsprung’s disease
verfasst von: Anne Marie O’Donnell
Hiroki Nakamura
Christian Tomuschat
Naoum Fares Marayati
Prem Puri
Publikationsdatum: 01.11.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Surgery International / Ausgabe 1/2019
Print ISSN: 0179-0358
Elektronische ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-018-4370-x

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Abnormal Scn1b and Fxyd1 gene expression in the pulled-through ganglionic colon may influence functional outcome in patients with Hirschsprung’s disease

Abstract

Purpose

Methods

Results

Conclusion

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