Resection of the abnormally innervated bowel is essential to avoid life threatening complications. Previous data showed despite successful surgical treatment, there was a large proportion of patients in whom constipation, soiling and abdominal pain persisted. After an average of 9 years, 53% of patients continued to suffer from fecal incontinence and 22% were still Ganetespib cancer constipated 2-4. The reasons for these persistent symptoms were not clear, although data were emerging to suggest that those with constipation have a neuropathy proximal to the aganglionic segment 5. Aganglionosis is attributed to a failure in the time-specific migration of enteric neural crest-derived cells into the intestinal tract.

Most studies on the pathogensis of HSCR were concerned on the autologous abnormity of migrating enteric neural precursors (ENPs), and the results showed that mutations of the RET, GDNF, EDNRB, SOX10, NRG1, NKX2-1 and EDN3 genes appeared to give dominant, recessive, or polygenic patterns of inheritance 6-9. However, research on target cells such as smooth muscle was rather limited. Smooth muscle thickening and intestinal wall remodeling existed in aganglionic and ganglionic segment of HSCR. But the influence of intestinal wall remodeling on prognosis of Hirschsprung disease, and the molecular pathways triggering the thickening and remodeling process are still poorly understood. Previous studies indicated that smooth muscle had a major impact on determining the number of innervating neurons. Jacob CL found that smooth muscle of the aganglionic colon was less favourable for neuronal development than that of normal colon and the mechanism was not clear [10].

Many proteins with abnormal function or expression level in the smooth muscle cells of the aganglionic part of the colon in HSCR have been identified, such as cholinoreceptors, alpha-smooth muscle isoactin, Semaphorin 3A, sarcoglycan subcomplex and Connexin43 etc 11- 17. These proteins participate in the pathogenesis through impairing intercellular communication between interstitial cells of Cajal and smooth muscle cells or altering the cytoskeleton in smooth muscle cells or disturbing the microenvironment around the targets of migrating neural crest cells in autocrine or paracrine manner during colon development. But the mechanism of the proteins in smooth muscle participated in intestinal dysfunction in HSCR patients has not been clarified. The FHL1 gene, located on chromosome Xq27.2, encodes four-and-a-half Carfilzomib LIM protein-1 (FHL1) and its spliced isoform, SLIMMER or FHL1C.