Effect of miR-155 Mediated by Wnt/β-catenin Signaling Pathway on Experssion of E-cadherin and Snail in Ulcerative Colitis / 华中科技大学学报(医学版)

ABSTRACT

Objective@#To detect changes of miR-155，Wnt/β-catenin，E-cadherin and snail in colon tissues of mice and to investigate the mechanism of miR-155 on epithelial-mesenchymal transition mediated by Wnt/β-catenin signaling pathway in ulcerative colitis（UC）. @*Methods@#Thirty-two C57 mice were randomly divided into 4 groups：normal group，model group，miR-155 antagomir group and negative control group. Except the normal group, each group was given 3% dextran sulfate sodium（DSS）for one week to prepare the UC model. From the fifth day，the miR-155 antagomir group and the negative control group were intraperitoneally injected with miR-155 antagomir and the negative control preparations（80 mg/kg weight）and the equal volume of phosphate buffered saline（PBS）were administered intraperitoneally in the normal group and the model group for three consecutive days. From the first day of modeling，mouse body weight changes，fecal traits，blood stools，etc. were recorded daily. On the eighth day, all the mice were sacrificed，and the disease activity index score（DAI）was measured；the length of colon tissue was measured；hematoxylin-eosin（HE）staining method was used to detect the pathological changes of colon tissue；in situ hybridization was used to detect miR-155 content in colon tissue；Real-time PCR，Western blotting and immunohistochemistry（IHC）were used to detect the expression of miR-155，Wnt1，β-catenin，Cyclin D1，E-cadherin and snail in colon tissues.@* Results@#Compared with the normal group，HE in the model group showed infiltrations of a large number of inflammatory cells，goblet cell reduction and arrangement disorder，mucosal defect and ulcer formation in the mucosa and submucosa of the colon tissue，and the DAI score was significantly increased（P<0.01）.The length of colon was significantly decreased（P<001），the content of miR-155 in colon tissue was significantly increased，and the expression levels of Wnt1，β-catenin，Cyclin D1 and snail mRNA and protein were significantly increased（P<0.01），but E-cadherin expression was significantly lower（P<0.01）；however，compared with the model group，HE in the miR155 antagomir group showed a significant improvement in colonic tissue lesions，a significant decrease in DAI score（P<0.01），and a significant increase in colon length（P<0.01）.The content of miR-155 in colon tissue was significantly decreased，and the expression levels of Wnt1，β-catenin，Cyclin D1 and snail mRNA and protein were significantly decreased（P<0.01），and the expression of E-cadherin was significantly increased（P<005） @*Conclusion@#MiR-155 can down-regulate E-cadherin and up-regulate snail expression，activate epithelial-mesenchymal transition，and induce aggravation of UC by activating Wnt/β-catenin signaling pathway.