Molecular mechanism of Polyphyllin Ⅶ inhibiting ectopic endometrial migration and invasion of adenomyosis by regulating epithelial-mesenchymal transition
Objective:To investigate the effect of polyphyllin Ⅶ(PPⅦ)on ectopic endometrial migration and invasion in adenomyosis(AM)by regulating epithelial mesenchymal transition(EMT).Methods:The key targets of PPⅦ in the intervention of AM were analysed by bioinformatics and verified by in vivo and in vitro experiments.The AM mouse model was established by drip feeding of tamoxifen and treated with PPⅦ.The study observed morphological and pathological changes in the uterus using hematoxylin-eosin(HE)staining,and detected the expressions of cadherin 1(CDH1),cadherin 2(CDH2)and matrix metalloproteinase 2(MMP2)in the uterus through immunohistochemistry.Additionally,AMDC were isolated and subsequently characterized by immunofluorescence.The activity,migration and invasion of AMDC were evaluated using CCK-8 and Transwell experiments to detect the effect of PPⅦ.RT-PCR and Western Blot were used to detect the expression of CDH1,CDH2 and MMP2.Results:The bioinformatics analysis yielded 381 PPⅦ targets and 1630 differentially expressed genes in AM.Enrichment analysis revealed that PPⅦ treatment of AM primarily involved key targets,including CDH1,CDH2,and MMP2,and significant biological processes,such as EMT and migration.In the in vivo experiments,the uterus in the model group exhibited redness,congestion,and enlargement compared to the blank group.The structure of the endometrial-myometrium was disordered,with endometrial glands invading the myometrium,and the expression of CDH1 significantly decreased(P＜0.01),CDH2 and MMP2 expression significantly-increased(P＜0.05,P＜0.01),compared with the blank group.Compared with the model group,both the mifepristone and PPⅦ groups reduced the number of endometrial glands invading the myometrium,increased the expression levels of CDH1,decreased CDH2 and MMP2(P＜0.05).In vitro experiments confirmed that AMDC exhibited mesenchymal properties.PPW inhibited the migration and invasive ability of AMDC,and had a dose-dependent effect on up-regulating the mRNA and protein expression levels of CDH1,and down-regulating CDH2 and MMP2.Conclusion:PPⅦ can inhibit the migration and invasion of AM ectopic endometrium by regulating the EMT process,which provides a new exploration direction and evidence support for the prevention and treatment of AM and the development of drugs.
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