Intracellular Wnt/Beta-Catenin Signaling Underlying 17beta-Estradiol-Induced Matrix Metalloproteinase 9 Expression in Human Endometriosis1

Ling Zhang, Xiong W, Wenqian Xiong, Xiong Y, Yao Xiong, Hengwei Liu, Liu H, Na Li, Li N, Yu Du, Du Y, Yi Liu, Liu Y
Biology of reproduction · 2016 · vol. 94(3) , pp. 70 · doi:10.1095/biolreprod.115.135574 · PMID:26888969 · W2275004114
article OA: bronze CC0 ⤵ 24 in-corpus citations
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This study found that 17beta-estradiol induces MMP9 expression in human endometrial stromal cells by promoting beta-catenin binding to the MMP9 promoter, suggesting a role in endometriosis.

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Abstract

Extracellular matrix remodeling is necessary for ectopic endometrium implantation. Many studies have shown an increased expression of matrix metalloproteinase 9 (MMP9) in the ectopic endometrium of endometriosis. However, the signaling pathways and cellular effects related to this process remain incompletely elucidated. The objective of our study was to investigate the association between MMP9 and the Wnt signaling pathway under the regulation of 17beta-estradiol (E2) in endometrial stromal cells. We found that MMP9 was elevated in tissues from women with endometriosis compared with normal women. Furthermore, MMP9 and beta-catenin increased concurrently in a time- and dose-dependent manner after E2 treatment. To clarify the relationship between MMP9 and beta-catenin, we performed luciferase promoter reporter and chromatin immunoprecipitation assays. A beta-catenin/TCF3/LEF1 complex bound to a specific site on the MMP9 promoter that promoted MMP9 gene and protein expression. The promotion of MMP9 by the Wnt signaling pathway under the regulation of E2 may contribute to the pathophysiology of this disease.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Estradiol Gene Expression Regulation Matrix Metalloproteinase 9 Wnt Signaling Pathway Adult beta Catenin beta Catenin beta Catenin Endometriosis Estradiol Estrogen Receptor alpha Estrogen Receptor alpha Estrogen Receptor alpha Female Gene Expression Regulation Humans Matrix Metalloproteinase 9 Matrix Metalloproteinase 9 Promoter Regions, Genetic

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