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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

Observation of colon tissue at 28 days after mesenchymal stem cell transplantation (MSCT) under microscope and fluorescent microscope. a Colon tissue lesion significantly improved after MSCT (hematoxylin and eosin, ×100). b The fluorescence signal could be observed in each layer of intestinal tissue (×100)
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Fig4: Observation of colon tissue at 28 days after mesenchymal stem cell transplantation (MSCT) under microscope and fluorescent microscope. a Colon tissue lesion significantly improved after MSCT (hematoxylin and eosin, ×100). b The fluorescence signal could be observed in each layer of intestinal tissue (×100)

Mentions: The result of flow cytometry showed that MSCs expressed CD44+ and CD54+ antigen markers. The positive cells of CD44+ were 89.6±6.0 %, and those of CD54+ were 95.5±3.9 % [12]. Well-grown MSCs with stable expression of GFP were cultured (Fig. 3) and then transplanted into established IBD rats. The pathological manifestations of IBD in the MSCT group were better than those in the IBD group; most ulcers were healed, but edema and inflammatory cell infiltration still existed (Fig. 4a). Under fluorescent microscope, MSCs labeled by GFP were populated in the damaged areas from the basement to the top of the fossae. GFP-positive cell density accounted for more than 50 % of the epithelial cells of the colorectal mucosa (Fig. 4b). In our previous study, the Sry gene and Y chromosome were detected by PCR and fluorescence in situ hybridization (FISH) to determine the location of male donor cells in the female colon after transplantation [12].Fig. 3


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)

Observation of colon tissue at 28 days after mesenchymal stem cell transplantation (MSCT) under microscope and fluorescent microscope. a Colon tissue lesion significantly improved after MSCT (hematoxylin and eosin, ×100). b The fluorescence signal could be observed in each layer of intestinal tissue (×100)
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Observation of colon tissue at 28 days after mesenchymal stem cell transplantation (MSCT) under microscope and fluorescent microscope. a Colon tissue lesion significantly improved after MSCT (hematoxylin and eosin, ×100). b The fluorescence signal could be observed in each layer of intestinal tissue (×100)
Mentions: The result of flow cytometry showed that MSCs expressed CD44+ and CD54+ antigen markers. The positive cells of CD44+ were 89.6±6.0 %, and those of CD54+ were 95.5±3.9 % [12]. Well-grown MSCs with stable expression of GFP were cultured (Fig. 3) and then transplanted into established IBD rats. The pathological manifestations of IBD in the MSCT group were better than those in the IBD group; most ulcers were healed, but edema and inflammatory cell infiltration still existed (Fig. 4a). Under fluorescent microscope, MSCs labeled by GFP were populated in the damaged areas from the basement to the top of the fossae. GFP-positive cell density accounted for more than 50 % of the epithelial cells of the colorectal mucosa (Fig. 4b). In our previous study, the Sry gene and Y chromosome were detected by PCR and fluorescence in situ hybridization (FISH) to determine the location of male donor cells in the female colon after transplantation [12].Fig. 3

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