Effects of Gentianopsis paludosa xanthone on the Expression of TGF-β1/Smad Pathway and EMT Factors during the Evolution of Ulcerative Colitis-related Intestinal Fibrosis to CAC in Rats
Objective:To investigate the effect of Gentianopsis Paludosa xanthone on the expression of transforming growth factor β1(TGF-β1)/Smad pathway and epithelial-mesenchymal transition(EMT)factors during the evolution of ulcerative colitis(UC)-related intestinal fibrosis to colitis-associated colorectal cancer(CAC)in rats.Methods:A total of 70 Wistar rats were randomly divided into normal control group,UC-related intestinal fibrosis model group,CAC model group,Gentianopsis paludosa xanthone 35,70 and 140 mg/kg groups,and thalidomide 14 mg/kg group,with 10 rats in each group.Except for normal control group,the remaining 60 rats were given TNBS via enemator to establish a UC-related intestinal fibrosis model,and then 50 rats were injected with DMH to establish a CAC model,of which 40 rats were treated with corresponding drugs.The disease activity index(DAI),colon length,wall thickness and colon wet mass index of rats were evaluated.The pathological changes of colon were observed by Masson staining.The protein expressions of TGF-β1 and phospho-smad2/3,and mRNA levels of E-cadherin(E-cad)and β-catenin were detected by Western blot and qPCR,respectively.The expression of Zinc finger protein Snail was detected by immunohistochemistry(IHC).Results:Compared with the normal control group,the CAC model group showed decreased colon length,increased wall thickness and colon wet mass index(P＜0.01),and well-differentiated adenomas were observed in the inner wall of the colon,as well as the protein expression of TGF-β1 and P-smad2/3 were decreased(P＜0.01).The mRNA level of E-cad was significantly down regulated,while the mRNA level of β-catenin was significantly up regulated(P＜0.01).The expression of Snail was elevated(P＜0.01).Compared with the CAC model group,the Gentianopsis paludosa xanthone 70 and 140 mg/kg groups showed increased colon length(P＜0.01)and decreased wall thickness,colon wet mass index and DAI score(P＜0.01 or P＜0.05).The collagen volume fraction was in-creased in the Gentianopsis paludosa xanthone 35,70 and 140 mg/kg groups(P＜0.01),but the differentiation degree of colon adenoma was reduced.In each drug treatment group,the protein expressions of TGF-β1 and P-smad2/3 and the E-cad mRNA level were up regulated(P＜0.01),,while the β-catenin mRNA level was down regulated,with reduced expression of Snail(P＜0.01).Conclusion:Gentianopsis paludo-sa xanthone can effectively inhibit the progression of UC-related intestinal fibers to CAC,possibly by promoting the expression of TGF-β1 and P-smad2/3 in the TGF-β1/smad pathway,and regulating the levels of EMT factors E-cad,β-catenin and Snail.
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