A role for Pten in paediatric intestinal dysmotility disorders.

Hdl Handle:
http://hdl.handle.net/10147/207402
Title:
A role for Pten in paediatric intestinal dysmotility disorders.
Authors:
O'Donnell, Anne-Marie; Puri, Prem
Affiliation:
National Children's Research Centre, Our Lady's Children's Hospital, Crumlin,, Dublin 12, Ireland.
Citation:
Pediatr Surg Int. 2011 May;27(5):491-3.
Journal:
Pediatric surgery international
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207402
DOI:
10.1007/s00383-010-2828-6
PubMed ID:
21258937
Abstract:
PURPOSE: The enteric nervous system (ENS) is a network of neurons and glia that lies within the gut wall. It is responsible for the normal regulation of gut motility and secretory activities. Hirschsprung's disease (HD) is a congenital defect of the ENS, characterised by an absence of ganglia in the distal colon. Intestinal neuronal dysplasia (IND) is a condition that clinically resembles HD, characterised by hyperganglionosis, giant and ectopic ganglia, resulting in intestinal dysmotility. Intestinal ganglioneuromatosis is characterised by hyperplasia and hypertrophy of enteric neuronal cells and causes chronic intestinal pseudo-obstruction (CIPO). Phosphatase and tensin homolog deleted on chromosome 10 (Pten) is a phosphatase that is critical for controlling cell growth, proliferation and cell death. A recent study of Pten knockout mice showed evidence of ganglioneuromatosis in the ENS suggesting a role for this protein in ENS development. Ganglioneuromatosis patients have also been shown to have a decreased level of Pten expression in the colon. The aim of our study was to investigate Pten expression in the ENS of HD and IND patients compared to normal controls. METHODS: Resected tissue from 10 HD and 10 IND type B patients was fixed and embedded in paraffin wax. Normal control colon tissue was obtained from ten patients who underwent a colostomy closure for imperforate anus. Sections were cut and immunohistochemistry was carried out using a Pten antibody. Results were analysed by light microscopy. RESULTS: Staining showed that Pten was strongly expressed in ganglia of both the submucosal and myenteric plexus of normal and HD specimens from the ganglionic colon. Pten expression was significantly reduced in the giant ganglia in IND patients in both the myenteric and submucosal plexuses compared to the normal controls. Specimens from the aganglionic region of HD did not show Pten expression. CONCLUSION: To the best of our knowledge, this is the first study demonstrating a marked reduction of Pten expression in the myenteric and submucous plexuses of IND patients. Neuronal Pten deficiency in IND may disrupt the chemical pathway associated with the proliferation and development of neuronal cells forming mature ganglia and thus cause motility dysfunction.
Language:
eng
MeSH:
Digestive System Abnormalities/*physiopathology; Enteric Nervous System/abnormalities; Gastrointestinal Motility/*physiology; Hirschsprung Disease/metabolism/*physiopathology; Humans; Immunohistochemistry; PTEN Phosphohydrolase/metabolism/*physiology
ISSN:
1437-9813 (Electronic); 0179-0358 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorO'Donnell, Anne-Marieen_GB
dc.contributor.authorPuri, Premen_GB
dc.date.accessioned2012-02-01T10:24:05Z-
dc.date.available2012-02-01T10:24:05Z-
dc.date.issued2012-02-01T10:24:05Z-
dc.identifier.citationPediatr Surg Int. 2011 May;27(5):491-3.en_GB
dc.identifier.issn1437-9813 (Electronic)en_GB
dc.identifier.issn0179-0358 (Linking)en_GB
dc.identifier.pmid21258937en_GB
dc.identifier.doi10.1007/s00383-010-2828-6en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207402-
dc.description.abstractPURPOSE: The enteric nervous system (ENS) is a network of neurons and glia that lies within the gut wall. It is responsible for the normal regulation of gut motility and secretory activities. Hirschsprung's disease (HD) is a congenital defect of the ENS, characterised by an absence of ganglia in the distal colon. Intestinal neuronal dysplasia (IND) is a condition that clinically resembles HD, characterised by hyperganglionosis, giant and ectopic ganglia, resulting in intestinal dysmotility. Intestinal ganglioneuromatosis is characterised by hyperplasia and hypertrophy of enteric neuronal cells and causes chronic intestinal pseudo-obstruction (CIPO). Phosphatase and tensin homolog deleted on chromosome 10 (Pten) is a phosphatase that is critical for controlling cell growth, proliferation and cell death. A recent study of Pten knockout mice showed evidence of ganglioneuromatosis in the ENS suggesting a role for this protein in ENS development. Ganglioneuromatosis patients have also been shown to have a decreased level of Pten expression in the colon. The aim of our study was to investigate Pten expression in the ENS of HD and IND patients compared to normal controls. METHODS: Resected tissue from 10 HD and 10 IND type B patients was fixed and embedded in paraffin wax. Normal control colon tissue was obtained from ten patients who underwent a colostomy closure for imperforate anus. Sections were cut and immunohistochemistry was carried out using a Pten antibody. Results were analysed by light microscopy. RESULTS: Staining showed that Pten was strongly expressed in ganglia of both the submucosal and myenteric plexus of normal and HD specimens from the ganglionic colon. Pten expression was significantly reduced in the giant ganglia in IND patients in both the myenteric and submucosal plexuses compared to the normal controls. Specimens from the aganglionic region of HD did not show Pten expression. CONCLUSION: To the best of our knowledge, this is the first study demonstrating a marked reduction of Pten expression in the myenteric and submucous plexuses of IND patients. Neuronal Pten deficiency in IND may disrupt the chemical pathway associated with the proliferation and development of neuronal cells forming mature ganglia and thus cause motility dysfunction.en_GB
dc.language.isoengen_GB
dc.subject.meshDigestive System Abnormalities/*physiopathologyen_GB
dc.subject.meshEnteric Nervous System/abnormalitiesen_GB
dc.subject.meshGastrointestinal Motility/*physiologyen_GB
dc.subject.meshHirschsprung Disease/metabolism/*physiopathologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunohistochemistryen_GB
dc.subject.meshPTEN Phosphohydrolase/metabolism/*physiologyen_GB
dc.titleA role for Pten in paediatric intestinal dysmotility disorders.en_GB
dc.contributor.departmentNational Children's Research Centre, Our Lady's Children's Hospital, Crumlin,, Dublin 12, Ireland.en_GB
dc.identifier.journalPediatric surgery internationalen_GB
dc.description.provinceLeinster-

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