TGF-β/snail-mediated epithelial-to-mesenchymal transition disrupts estradiol metabolism through suppressing the HSD17B2 expression in endometriotic epithelial cells

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The study investigated how TGF-β/snail-mediated epithelial-to-mesenchymal transition disrupts estradiol metabolism by suppressing HSD17B2 expression in endometriotic epithelial cells.

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Abstract

Endometriosis affects nearly 10 % of reproductive-age women and is characterized by the growth of endometrial-like tissues outside the uterus. This disease poses significant diagnostic and therapeutic challenges due to its unknown origins and complex pathophysiology. Our study investigates how epithelial-mesenchymal transition (EMT) contributes to the dysregulation of estradiol metabolism by suppressing hydroxysteroid 17β dehydrogenase 2 (HSD17B2) expression in endometriotic epithelial cells. We used Gene Set Variation Analysis (GSVA) on public microarray data to correlate EMT scores with HSD17B2 levels. This approach revealed a significant correlation, showing that EMT is linked to reduced HSD17B2 expression in endometriotic tissues. Furthermore, our qPCR and immunoblotting results showed that TGF-β-induced EMT significantly reduced HSD17B2 expression in human endometriotic 12Z epithelial cells. Additionally, our data showed that Snail, an EMT-related transcription factor, acts on the E-box motif in the HSD17B2 promoter to suppress transcription. Our findings show that EMT is associated with decreased HSD17B2 expression in endometriotic tissues. This downregulation disrupts estradiol metabolism, possibly contributing to endometriosis pathogenesis. Our study offers critical insights into the molecular mechanisms of endometriosis and suggests that targeting EMT, especially the TGF-β/Snail axis, could provide a new therapeutic approach.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium Endometrium Endometrium Endometrium

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europepmc
last seen: 2026-06-13T17:20:28.795615+00:00
openalex
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pubmed
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