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

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

Stem Cell Research & Therapy, May 2015

25998108

Yanfen Xing, Xiaojie Chen, Yanwen Cao, Jianyun Huang, Xuhong Xie, Yaming Wei

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). 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) was used to establish IBD in a rat model. 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 qRT-PCR in the IBD rat model on day14 and day 28 after transplantation. 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 up-regulated, and 197 down-regulated in the MSC-transplanted group compared with the IBD control group. Real-time quantitative PCR results showed that the level of Olfm4 mRNA expression in the IBD group (2.54 ± 0.20) was significantly increased compared to 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-3β mRNA was decreased in the setting of inflammation (0.65 ± 0.04 vs. 1.00 ± 0.01 at ns, P < 0.05), but returned to normal levels after MSCT (0.81 ± 0.17). The expression of β-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. 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.