Altered expression of AKT1 and P38A in the colons of patients with Hirschsprung's disease.

Purpose: Hirschsprung's disease (HSCR) is a functional obstruction of the gastrointestinal tract due to the congenital absence of enteric ganglion cells. The proto-oncogene RET is one of the primary genes implicated in the aetiology of HSCR. We designed this study to investigate the expression of 10 RET regulatory network genes in the colons of patients with HSCR.

Methods: HSCR tissue specimens (n = 28) were collected at the time of pull-through surgery. qPCR analysis was applied to compare the expression levels of 10 genes in the RET regulatory network. Western blot analysis was performed to quantify the protein expression. Immunohistochemistry was performed to determine the localization of AKT1 and P38A in HSCR colon tissue.

Results: AKT1 (p = 0.015) and P38A (p = 0.039) were both significantly downregulated in the aganglionic segment compared to those in the ganglionic segment in HSCR patients (n = 28). Western blot analysis revealed the decreasing protein expression of AKT1 and P38A in the aganglionic segment compared to ganglionic segment and control colon tissues (p < 0.05). Immunohistochemistry staining revealed that both AKT1 and P38A were localized in the colonic mucosa and were significantly decreased in the aganglionic segment.

Conclusion: To our knowledge, we report for the first time the expression of RET regulatory network genes in the colons of patients with HSCR. The markedly decreased expression of AKT1 and P38A suggested a possible role in HSCR pathogenesis.