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

Xing Y, Chen X, Cao Y, Huang J, Xie X, Wei Y - Stem Cell Res Ther (2015)

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Blood Transfusion, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1. Panfu Road, Guangzhou, 510180, Guangdong Province, China. 398340944@qq.com.

ABSTRACT

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-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.

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.

No MeSH data available.


Related in: MedlinePlus

Expression of atonal homolog 1 (Atoh1) and olfactomedin 4 (Olfm4) genes in inflammatory bowel disease (IBD) rats at 14 days after treatment with mesenchymal stem cell transplantation (MSCT). a Expression of Atoh1 in MSCT group upregulated in comparison with the other groups. b Expression of Olfm4 increased in IBD group. MSC, mesenchymal stem cell. *P<0.05
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Fig5: Expression of atonal homolog 1 (Atoh1) and olfactomedin 4 (Olfm4) genes in inflammatory bowel disease (IBD) rats at 14 days after treatment with mesenchymal stem cell transplantation (MSCT). a Expression of Atoh1 in MSCT group upregulated in comparison with the other groups. b Expression of Olfm4 increased in IBD group. MSC, mesenchymal stem cell. *P<0.05

Mentions: Atoh1 and olfactomedin 4 (Olfm4) were associated with the Notch signaling pathway, which regulated cell proliferation and differentiation [18, 19]. The expression of Atoh1 in the MSCT group was significantly higher than in the MSC (1.34±0.27 versus 0.95±0.08, P = 0.011), normal (1.34±0.27 versus 0.91±0.15, P = 0.004), or IBD rat models (1.34±0.27 versus 0.99±0.48, P = 0.007) (there were no significant differences among these three groups). The expression of Olfm4 in MSCT rats was downregulated in comparison with IBD rats (P <0.05). No difference was found when compared with normal rats (P >0.05) (Table 4, Fig. 5).Table 4


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

Xing Y, Chen X, Cao Y, Huang J, Xie X, Wei Y - Stem Cell Res Ther (2015)

Expression of atonal homolog 1 (Atoh1) and olfactomedin 4 (Olfm4) genes in inflammatory bowel disease (IBD) rats at 14 days after treatment with mesenchymal stem cell transplantation (MSCT). a Expression of Atoh1 in MSCT group upregulated in comparison with the other groups. b Expression of Olfm4 increased in IBD group. MSC, mesenchymal stem cell. *P<0.05
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4487973&req=5

Fig5: Expression of atonal homolog 1 (Atoh1) and olfactomedin 4 (Olfm4) genes in inflammatory bowel disease (IBD) rats at 14 days after treatment with mesenchymal stem cell transplantation (MSCT). a Expression of Atoh1 in MSCT group upregulated in comparison with the other groups. b Expression of Olfm4 increased in IBD group. MSC, mesenchymal stem cell. *P<0.05
Mentions: Atoh1 and olfactomedin 4 (Olfm4) were associated with the Notch signaling pathway, which regulated cell proliferation and differentiation [18, 19]. The expression of Atoh1 in the MSCT group was significantly higher than in the MSC (1.34±0.27 versus 0.95±0.08, P = 0.011), normal (1.34±0.27 versus 0.91±0.15, P = 0.004), or IBD rat models (1.34±0.27 versus 0.99±0.48, P = 0.007) (there were no significant differences among these three groups). The expression of Olfm4 in MSCT rats was downregulated in comparison with IBD rats (P <0.05). No difference was found when compared with normal rats (P >0.05) (Table 4, Fig. 5).Table 4

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Blood Transfusion, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1. Panfu Road, Guangzhou, 510180, Guangdong Province, China. 398340944@qq.com.

ABSTRACT

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-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.

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.

No MeSH data available.


Related in: MedlinePlus