Comparative proteomics of Hirschsprung's disease.

UNLABELLED: Hirschsprung's disease (HSCR) is a developmental disorder of the enteric nervous system characterized by aganglionosis in distal gut. The estimated population incidence of HSCR is 1/5000 live births, but higher in Asian populations. As the disease mainly manifested bowel motility disturbance, the underlying mechanism is unknown. Furthermore, in the long term up to 75% of patients showed unsatisfactory postoperative bowel function like incontinence or constipation, and 10% required a permanent colostomy. Improved therapy of HSCR is required, but the pathophysiological mechanism for postoperative bowel dysfunction is not clear. In this study, we perform a proteomics study in HSCR patients, expecting some findings in protein alterations to provide more information to reveal the pathophysiological mechanisms of disturbed bowel function before and after surgery therapy. As a result, we identified 16 proteins expressed differently in aganglionic segment of HSCR patients. These proteins function diversely, and included cytoskeleton proteins, regulatory proteins and some enzymes.

BIOLOGICAL SIGNIFICANCE: In the present study, we performed a 2-DE based proteomic research on HSCR patients, in order to find some clue for the pathomechanism of bowel motility of HSCR disease. As a character of this study, we also compared the expression of altered proteins in ganglionic segment of HSCR patients with that in normal children. Our results showed that some altered proteins found in aganglionic segment had also changed their expression in ganglionic segment comparing with normal children. This result suggested that the ganglionic segment of HSCR patients was not completely normal, and this is important because it provided more information to understand the pathophysiological mechanisms of bowel dysfunction and will help to the therapy of HSCR disease.