Altered expression of a two-pore domain (K2P) mechano-gated potassium channel TREK-1 in Hirschsprung's disease.
Pediatr Res
; 80(5): 729-733, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27384506
ABSTRACT
BACKGROUND:
The pathophysiology of Hirschsprung's disease (HSCR) is not fully understood. A significant proportion of patients have persisting bowel symptoms such as constipation, soiling, and enterocolitis despite correctly performed operations. Animal data suggest that stretch-activated 2-pore domain K+ channels play a critical role in the maintenance of intestinal barrier integrity.METHODS:
We investigated TREK-1 protein expression in ganglionic and aganglionic regions of HSCR patients (n = 10) vs. normal control colon (n = 10). Protein distribution was assessed by using immunofluorescence and confocal microscopy. Gene and protein expression were quantified using quantitative real-time polymerase chain reaction, western blot analysis, and densitometry.RESULTS:
Confocal microscopy of the normal colon revealed strong TREK-1 channel expression in the epithelium. TREK-1-positive cells were decreased in aganglionic and ganglionic bowel compared to controls. TREK-1 gene expression levels were significantly decreased in aganglionic and ganglionic bowel compared to controls (P < 0.05). Western blotting revealed decreased TREK-1 protein expression in aganglionic and ganglionic bowel compared to controls.CONCLUSION:
We demonstrate, for the first time, the expression and distribution of TREK-1 channels in the human colon. The decreased TREK-1 expression in the aganglionic and ganglionic bowel observed in HSCR may alter intestinal epithelial barrier function leading to the development of enterocolitis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio de Domínios Poros em Tandem
/
Doença de Hirschsprung
Tipo de estudo:
Observational_studies
Limite:
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Pediatr Res
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Irlanda