Details

Autor(en) / Beteiligte

• Tomuschat, Christian
• O'Donnell, Anne Marie
• Coyle, David
• Puri, Prem

Titel

Increased protease activated receptors in the colon of patients with Hirschsprung's disease

Ist Teil von

• Journal of pediatric surgery, 2020-08, Vol.55 (8), p.1488-1494

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• The pathophysiology of Hirschsprung's associated enterocolitis (HAEC) is not understood. Abnormal intestinal motility and altered intestinal epithelial barrier function have been suggested to play a key role in the causation of HAEC. Protease-activated receptors (PARs) 1 and 2, have been implicated in inflammatory reactions, intestinal permeability and modulation of motility in the gut. We investigated PAR-1 and PAR-2 protein expression in aganglionic and ganglionic regions of patients with Hirschsprung's Disease (HSCR) (n = 10) versus 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 (qPCR), western blot analysis, and densitometry. qPCR and Western blot analysis revealed that PAR-1 and PAR-2 expression was significantly increased in ganglionic and aganglionic bowel in HSCR compared to controls (p < 0.003). Confocal microscopy revealed strong PAR-1 and PAR-2 expression in smooth muscles, interstitial cells of Cajal (ICCs), platelet-derived growth factor-alpha receptor-positive (PDGFRα+) cells, enteric neurons and epithelium in the ganglionic and aganglionic bowel compared to controls. Increased PAR-1 and PAR-2 expression in the colon of patients with HSCR suggests that excessive local release of PAR activating proteases may trigger inflammatory responses leading to HAEC.