Abstract
IntroductionThe 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).MethodsTNBS (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.ResultsThe 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-3β 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 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.ConclusionsThe 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.
Highlights
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)
We explored the differential expression of genes associated with the Wnt and Notch signaling pathways in MSCT of an IBD rat model
There were no differences in the expression of Frizzled family receptor 3 (Fzd3), TCF4, and c-myc between IBD model rats and the normal group (Table 5, Fig. 6)
Summary
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). Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn’s disease (CD). These conditions produce recurrent chronic inflammatory illnesses of the intestinal. Mesenchymal stem cells (MSCs) have proliferation, differentiation, and engraftment capacity in appropriate target tissues [8]. We confirmed by in situ hybridazation and immunohistochemistry that allogenic transplanted hematopoietic stem cells or MSCs could populate the injured regions of the colon [12]. MSCs stimulated progenitor cells to improve epithelial renewal and engrafted in the damage tissues and even differentiated into colonic interstitial cells [13]. We do not know which genes and pathways are involved in reparation of the mucosa and transformation into intestinal epithelial cells
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