title: Expression of Wnt and Notch signaling pathways in inflammatory bowel disease treated with mesenchymal stem cell transplantation: evaluation in a rat model.
abstract: BACKGROUND
  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.
authors.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.|Guangdong Key laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1. Panfu Road, Guangzhou, 510180, Guangdong Province, China. 398340944@qq.com.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Department of Blood Transfusion, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1. Panfu Road, Guangzhou, 510180, Guangdong Province, China. chenxiao_j@163.com.|Guangdong Key laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1. Panfu Road, Guangzhou, 510180, Guangdong Province, China. chenxiao_j@163.com.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Chen
authors.affiliation: Guangdong Key laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1. Panfu Road, Guangzhou, 510180, Guangdong Province, China. caoyanwen2007@163.com.|Department of Gastroenterology, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1. Panfu Road, Guangzhou, 510180, Guangdong Province, China. caoyanwen2007@163.com.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Blood Transfusion, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1. Panfu Road, Guangzhou, 510180, Guangdong Province, China. jianyunhuang@126.com.|Guangdong Key laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1. Panfu Road, Guangzhou, 510180, Guangdong Province, China. jianyunhuang@126.com.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Blood Transfusion, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1. Panfu Road, Guangzhou, 510180, Guangdong Province, China. gdpueducn@126.com.|Guangdong Key laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1. Panfu Road, Guangzhou, 510180, Guangdong Province, China. gdpueducn@126.com.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Blood Transfusion, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1. Panfu Road, Guangzhou, 510180, Guangdong Province, China. weiyaming@163.com.|Guangdong Key laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, No. 1. Panfu Road, Guangzhou, 510180, Guangdong Province, China. weiyaming@163.com.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D059467:Transcriptome; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D051880:Receptors, Notch; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C502412:Wnt11 protein, rat; C491837:Wnt5a protein, rat; D051176:beta Catenin; D016179:Granulocyte Colony-Stimulating Factor; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3