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

Abstract Purpose 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. Methods 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. Results 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  Conclusion 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.