But whether or Cisplatin FDA not other proteins in smooth muscle participate in intestinal dysfunction in HSCR patients is not clear. In this study we found that circular muscle layer and longitudinal muscle layer were thickening at different extent in aganglionic and ganglionic segment of HSCR and the arrangement of circular muscle layer in aganglionic segment of HSCR was disorganized (Fig.(Fig.1).1). FHL1 was expressed in the ganglion cells of the myenteric plexus, submucosa, as well as in the longitudinal and circular muscle layer of the ganglionic colon. FHL1 expression level in ganglionic colon or aganglionic colon was significantly higher than that in normal colons. Meanwhile, we found FHL1 expression in aganglionic colon was slightly stronger than that in ganglionic colon.

Four and a half LIM domains protein 1 (FHL1) is the most widely expressed member of the FHL family of proteins, consisting of four and a half highly conserved LIM domains 35. LIM domains have been observed to act as modular protein-binding interfaces mediating protein-protein interactions in the cytoplasm and the nucleus 36. Northern blot analysis confirmed strikingly high expression of Fhl1 in skeletal muscle and heart, with considerably lower expression levels observed in several other tissues, including the colon, small intestine, and prostate. FHL1 mutations have been identified in a spectrum of human skeletal and cardiac muscle diseases 21-24. FHL1 could alter cytoskeleton and cell shape by binding with PDZ and LIM domain protein 1 (PDLIM1), Gelsolin (GSN), gamma-actin (ACTG) and a-actin (ACTN1) 37,38.

In rat aortic smooth muscle cells (SMCs) FHL1 knockdown could significantly inhibit the proliferation of SMCs but exerted no significant effect on cell apoptosis 25. Kwapiszewska G demonstrated that inhibition of Fhl-1 expression by siRNA significantly decreased pulmonary artery SMCs migration and proliferation, suggesting that Fhl1 was the key factor triggering the vascular remodeling process in pulmonary hypertension 26. Protein-protein interactions were critical for the normal membrane trafficking, localization, and function of voltage-gated ion channels. Immunoprecipitation experiments confirmed a physical interaction of FHL1 with the K (+) channel (KCNA5) complex in human atrium. With coexpression of FHL1, K (+) current density was markedly increased in atrial myocytes 39,40.

Data suggested that the alteration of delayed rectifier (IK) K+ current and Kv1.2 expression in DRG neurons from Irritable bowel syndrome (IBS) model rats represented a molecular mechanism underlying visceral pain and hyperexcitability in IBS 41. In the study of chronic stress-induced colonic hypermotility, Ying Liu found that GSK-3 repeated water avoidance stress (WAS) treatment resulted in up-regulation of Kir6.1 and SUR2B of KATP channels in the colon devoid of mucosa and submucosa 42.