Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 28, 2016; 22(12): 3335-3340
Published online Mar 28, 2016. doi: 10.3748/wjg.v22.i12.3335
Deficiency of platelet-derived growth factor receptor-α-positive cells in Hirschsprung's disease colon
Anne-Marie O’Donnell, David Coyle, Prem Puri
Anne-Marie O’Donnell, David Coyle, Prem Puri, National Children’s Research Centre, Our Lady’s Children’s Hospital Crumlin, 12 Dublin, Ireland
Author contributions: O’Donnell AM and Puri P contributed to study conception and design; O’Donnell AM and Coyle D contributed to specimen collection, and carried out the experimental work; O’Donnell AM, Coyle D and Puri P contributed to drafting the manuscript and have all read and approved the final draft.
Supported by National Children’s Research Centre/Children’s Medical Research Foundation, Ireland.
Institutional review board statement: The study was reviewed and approved by the Ethics (Medical Research) Committee of Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland, Ref. GEN/292/12.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: Dataset is available from the corresponding author at prem.puri@ncrc.ie.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Prem Puri, MS, FRCS, FRCS (Ed), FACS, FAAP (Hon.), DSc (Hon.), Professor, National Children’s Research Centre, Our Lady’s Children’s Hospital Crumlin, 12 Dublin, Ireland. prem.puri@ucd.ie
Telephone: +353-1-4096420
Received: October 6, 2015
Peer-review started: October 8, 2015
First decision: November 5, 2015
Revised: November 19, 2015
Accepted: December 19, 2015
Article in press: December 21, 2015
Published online: March 28, 2016
Processing time: 168 Days and 21.7 Hours
Abstract

AIM: To investigate whether the expression of platelet-derived growth factor receptor-α-positive (PDGFRα+)-cells is altered in Hirschsprung’s disease (HD).

METHODS: HD tissue specimens (n = 10) were collected at the time of pull-through surgery, while colonic control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 10). Immunolabelling of PDGFRα+-cells was visualized using confocal microscopy to assess the distribution of these cells, while Western blot analysis was undertaken to quantify PDGFRα protein expression.

RESULTS: Confocal microscopy revealed PDGFRα+-cells within the mucosa, myenteric plexus and smooth muscle in normal controls, with a marked reduction in PDGFRα+-cells in the HD specimens. Western blotting revealed high levels of PDGFRα protein expression in normal controls, while there was a striking decrease in PDGFRα protein expression in the HD colon.

CONCLUSION: These findings suggest that the altered distribution of PDGFRα+-cells in both the aganglionic and ganglionic HD bowel may contribute to the motility dysfunction in HD.

Keywords: Platelet-derived growth factor receptor alpha; Hirschsprung’s disease; Gastrointestinal motility; Aganglionosis; Myenteric plexus

Core tip: Hirschsprung’s disease is a congenital condition characterised by an absence of ganglia in the distal colon. Platelet-derived growth factor receptor-α-positive (PDGFRα+)-cells are a novel cell type recently found to be involved in gastrointestinal neurotransmission and smooth muscle contractility. Our study has revealed a striking decrease in PDGFRα+-cell expression in Hirschsprung’s disease colon compared to normal control colon. These results suggest an exciting new role for PDGFRα+-cells in the pathophysiology of this complex condition.