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Pediatric Surgery International

Published in:

01-11-2015 | Original Article

Rho-kinase expression in Hirschsprung’s disease

Authors: David Coyle, Anne Marie O’Donnell, Nicolae Corcionivoschi, John Gillick, Prem Puri

Published in: Pediatric Surgery International | Issue 11/2015

Abstract

Background

Rho-kinase (ROCK) is the primary effector protein in the RhoA pathway, which regulates Ca²⁺-independent smooth muscle contraction in the human bowel. This pathway has been reported to be hyper-activated in the aganglionic bowel of EDNRB-null (−/−) rats compared to the ganglionic bowel from EDNRB (+/+) rats. We hypothesised that ROCK expression is up-regulated in human aganglionic bowel and designed this study to investigate ROCK 1 and ROCK 2 expression in Hirschsprung’s disease (HSCR) and controls.

Materials and methods

Full-length specimens were collected following pull-through surgery for HSCR (n = 9). Colonic controls (n = 6) were obtained during colostomy closure from patients with anorectal malformations. Distribution of ROCK 1/2 expression was evaluated using double-labelled immunofluorescence and confocal microscopy. ROCK1/2 protein expression was assessed in mucosa and tunica muscularis using western blot analysis.

Results

There was strong expression of both ROCK 1 and ROCK 2 in interstitial cells of Cajal (ICCs) and ganglia. ROCK 1 expression was reduced in aganglionic bowel compared to HSCR ganglionic bowel and controls in both mucosa and tunica muscularis. ROCK 2 expression was similar in the colon of children with HSCR and controls.

Conclusions

This is the first report of strong ROCK expression in colonic ICCs. Although the rat model of aganglionic bowel suggests that Ca²⁺-independent smooth muscle contraction involving ROCK is hyper-activated, our data indicate ROCK 1 expression is decreased in aganglionic bowel and ROCK 2 expression is unaltered in children with HSCR.

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Title: Rho-kinase expression in Hirschsprung’s disease
Authors: David Coyle
Anne Marie O’Donnell
Nicolae Corcionivoschi
John Gillick
Prem Puri
Publication date: 01-11-2015
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Surgery International / Issue 11/2015
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-015-3762-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Rho-kinase expression in Hirschsprung’s disease

Abstract

Background

Materials and methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Materials and methods

Results

Conclusions

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