However whether FHL1 in kinase inhibitor MEK162 smooth muscle (SM) cells (the final effector organ) influences intestinal motility in HSCR patients or its mechanism in this process has not been clarified. Our results and all the above-mentioned data suggested that up-regulated expression level of FHL1 in ganglionic colon or aganglionic colon in HSCR might be associated with smooth muscle thickening and intestinal wall remodeling in HSCR through increasing the proliferation of smooth muscle cell or altering its skeleton. Furthermore when up-expressed FHL1 in smooth muscle cell, K (+) current density would also be markedly increased, like in atrial myocytes, thus changing their response to an electrical stimulus provided by the neighboring ICC.
In summary we hypothesize that FHL1 in smooth muscle (SM) cells (the final effector organ) could influence intestinal motility in HSCR patients by remodeling intestinal wall and changing their electrical response to stimulus provided by the neighboring ICC. Moreover since this experiment revealed that FHL1 expression in ganglionic colon, reserved in the operation, was much higher than that in the normal colon from newborn infants died from non-nervous or digestive system diseases, we believed that molecular abnormity also existed in this relatively normal colon in HSCR. So after resection of the affected aganglionic bowel segment, constipation, soiling and abdominal pain (intestinal dysfunction) are the subsequent problems in some children after pull-through surgery for Hirschsprung’s disease (HSCR).
In further research we intend to screen gene abnormity in ganglionic colon in HSCR and investigate the mechanism of intestinal dysfunction existing after surgery which will provide a fresh clue for clinical therapy for HSCR. Acknowledgments This study was supported by National Natural Science Foundation of China (81070538, 81100434 and 81200481), Specialized Research Fund for the Doctoral Program of Higher Education (20102104120014, 20092104120010) and Scientific Research Fund of Liaoning Provincial Education Department (L2010637). We would like to express our gratitude to all the subjects who participated in the study. Abbreviations HSCR Hirschsprung’s Disease SMC smooth muscle cells FHL1 four-and-a-half LIM protein-1 ENPs enteric neural precursors ENS enteric nervous system ICC interstitial cells of Cajal PDLIM1 PDZ and LIM domain protein 1 GSN Gelsolin ACTN1 a-actin.
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