Expression of Wnt and Notch signaling pathways in inflammatory bowel disease treated with mesenchymal stem cell transplantation: evaluation in a rat model

Introduction: The purpose of this study was to investigate the expression of Wnt and Notch signaling pathway-related genes in inflammatory bowel disease (IBD) treated with mesenchymal stem cell transplantation (MSCT). Methods: TNBS (2,4,6-trinitrobenzene sulfonic acid) was used to establish IBD in a rat model. Mesenchymal stem cells (MSCs) were transplanted via tail vein transfusion. Saline water was used in a control group. The expression of Wnt and Notch main signaling molecules was screened by gene chips and verified by quantitative reverse transcription-polymerase chain reaction in the IBD rat model on day 14 and day 28 after transplantation. Results: The IBD rat models were successfully established and MSCs were transplanted into those models. Genome-wide expression profile chips identified a total of 388 differentially expressive genes, of which 191 were upregulated and 197 were downregulated in the MSC-transplanted group in comparison with the IBD control group. Real-time quantitative polymerase chain reaction results showed that the level of Olfm4 mRNA expression in the IBD group (2.54+/-0.20) was significantly increased compared with the MSCT group (1.39+/-0.54) and the normal group (1.62+/-0.25) (P < 0.05). The Wnt3a mRNA was more highly expressed in IBD rats (2.92+/-0.94) and decreased in MSCT rats (0.17+/-0.63, P < 0.05). The expression of GSK-3 beta mRNA was decreased in the setting of inflammation (0.65+/-0.04 versus 1.00+/-0.01 in normal group, P < 0.05) but returned to normal levels after MSCT (0.81+/-0.17). The expression of beta-catenin was observed to increase in IBD tissues (1.76+/-0.44) compared with normal tissues (1.00+/-0.01, P < 0.05), but no difference was found in the MSCT group (1.12+/-0.36). Wnt11 declined at 14 days and returned to normal levels at 28 days in the IBD group; in comparison, a significantly lower expression was found in MSCT rats. There were no differences in the expression of Fzd3, c-myc, TCF4, and Wnt5a in inflammation, but all of those genes declined after MSCT treatment. Conclusions: The canonical Wnt and Notch signaling pathways are activated in IBD and may be suppressed by stem cell transplantation to differentiate into intestinal epithelium after MSCT. Moreover, the non-canonical Wnt signaling may be inhibited by canonical Wnt signaling in the setting of inflammation and may also be suppressed by MSCT.