BMP/Smad Signaling Pathway With Hirschsprung's Disease

Objectives Hirschsprung's disease(Hirschsprung's Disease, HD) are common in children with enteric nervous system defects, intestinal ganglion cell deficiency as the main feature of the digestive tract developmental abnormalities. Present studies suggest that neural crest cells in the development process can not be colonized with the intestinal,that impact of the development of the enteric nervous system, eventually lead no ganglion cells in disease incidence, the precise mechanism of HD is currently unknown, and it is one hots pot of research work in surgery. Regulation recent study found that bone morphogenetic proteins(bone morphogenetic proteins, BMPs) is considered an important protein involved in the enteric nervous system development, BMP / Smad signaling pathway in various stages of the developing nervous system of the enteric nervous system developed plays a key role. This study aims to determine the relative content of BMP-4 and Smad1 of the normal, expanding segment, transitional segment and spastic segment in the HD patients. Comparison of each group BMP4 and Smad1 expressions and explore BMP / Smad signaling pathway the role and relationship in etiology.Materials and Methods 1.In this study, all specimens were attained from 47 patients with confirmed pathologieal diagnosis of HD, in the surgery department of affiliated Hospital of Fujian Provincial Maternity and Child Care Center between 2013.3 and 2015.3. 2.All specimens were used the SP immunostaining with BMP-4 and Smad1 protein.The normal tissue of samples as normal controls, PBS instead of primary antibody as a negative control and the results were made quantitative and qualitative analysis and scanned. 3. Westernblot and RT-PCR:Separated samples intestines 1cm, after washing with PBS, placed in EP tube at-80? to Westernblot or RT-PCR detection. 4. Statistical Analysis: The groups were compared using chi-square test, correlation analysis using Pearson correlation test, test level a = 0.05, p <0.05 when statistically significant.Results Clinical analysis showed that BMP-4 and Smad1 were expressed in ganglion cells of HD, there were no obvious difference in muscular layers(P>0.05). the expression in structural segment was highly decreased the dilated segment(P<0.05), and no evident difference between normal segment and dilated segment(P>0.05). There was Positive correlation between BMP-4 and Smad1(r=0.671, P<0.05).Conclusions BMP-4 and Smad1 expression of lesions abnormal bowel segment in HD, Suggesting that it may be involved in the enteric nervous system maturation.The decrease in the aganglionic bowel implies that they maybe participate in the formation and maturation of enteric nervous system.