Abnormal distribution of sarcoglycan subcomplex in colonic smooth muscle cells of aganglionic bowel

Hirschsprung's disease (HD) is a development disorder of the enteric nervous system in which the altered innervation explains the inability of the aganglionic segment to relax. Impairment of cytoskeleton in SMC of aganglionic bowel has been shown. Sarcoglycan subcomplex (SG) may support the development and maintenance of muscle cells. We examined the SG subunit expression in colonic aganglionic and ganglionic specimens obtained from patients with HD. Full-thickness bowel specimens were obtained from six patients with HD. Six normal colon specimens were used as controls. Immunofluorescent analysis and reverse transcriptase polymerase chain reaction evaluation were performed for α-, β-, γ-, δ- and ε-SG. In control colon, the indirect immunofluorescence showed a strong staining pattern of β- γ- δ- and ε-SG while a weak positivity of α-SG was recorded. In aganglionic bowel, immunofluorescence intensity values documented a significant lack of ε-SG while an enhanced α-SG, coupled to a loss of ε-SG, was recorded in ganglionic bowel in HD-affected patients. Our observations underscore the assumption that non-neuronal elements of the colon might play a key role in the pathogenesis of HD and loss of ε-SG might critically alter the cytoskeleton in the aganglionic bowel segment. Up-regulation of α-SG is probably an acquired phenomenon to reinforce the sarcolemma and to perform a forceful contraction in dilated ganglionic HD-affected colon, related to chronic pseudo-obstruction, contributing to the intestinal dysmotility that persists in 20% of patients after resection of the aganglionic bowel.