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Deciphering the Role of ZEB1 as a Central Regulator of Epithelial-Mesenchymal Transition and Hormonal Resistance in Endometriosis.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Deciphering the Role of ZEB1 as a Central Regulator of Epithelial-Mesenchymal Transition and Hormonal Resistance in Endometriosis.
Συγγραφείς: Shirodkar S; Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, 9819771515, India., Doshi G; Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, 9819771515, India. gaurav.pharmacology@gmail.com.
Πηγή: Reproductive sciences (Thousand Oaks, Calif.) [Reprod Sci] 2026 Oct; Vol. 33 (10), pp. 1954-1977. Date of Electronic Publication: 2026 Sep 09.
Τύπος έκδοσης: Journal Article; Review
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Springer Country of Publication: United States NLM ID: 101291249 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1933-7205 (Electronic) Linking ISSN: 19337191 NLM ISO Abbreviation: Reprod Sci Subsets: MEDLINE
Imprint Name(s): Publication: 2020- : [New York] : Springer
Original Publication: Thousand Oaks, Calif. : Sage
Ιατρικοί όροι (MeSH): Zinc Finger E-box-Binding Homeobox 1*/metabolism , Zinc Finger E-box-Binding Homeobox 1*/genetics , Endometriosis*/metabolism , Endometriosis*/pathology , Endometriosis*/genetics , Epithelial-Mesenchymal Transition*/physiology , Endometrium*/metabolism , Endometrium*/pathology , Endometrium*/abnormalities, MicroRNAs/metabolism ; Humans ; Female ; Animals ; Signal Transduction ; Uterine Diseases
Περίληψη: Endometriosis is a chronic inflammatory and sex steroid hormone-dependent gynaecologic disease, characterised by endometrial cell proliferation outside the uterine cavity, often accompanied by fibrosis, progesterone resistance, and high recurrence despite hormonal and surgical interventions. Epithelial-mesenchymal transition (EMT) is important for establishment of lesions and invasiveness, but the upstream transcriptional regulators that integrate hormonal, inflammatory and epigenetic signals are incompletely defined. This review emphasises ZEB1 as a molecular integrator at the systems level in endometriosis pathogenesis. We reviewed evidence for selective upregulation of ZEB1 in ectopic lesions, where it inhibits epithelial adhesion molecules, stabilises mesenchymal differentiation and activates the attachment-invasion angiogenesis cascade required for lesion persistence. In addition to EMT, we discuss bidirectional crosstalk between ZEB1 and endocrine signalling, illustrating how oestrogen-mediated induction and suppression of progesterone receptor pathways converge to establish progesterone resistance. The review includes miR-200 family members, long non-coding RNAs and circular RNAs that strengthen ZEB1 expression through multilayered feedback mechanisms that perpetuate chronic inflammatory and pro-fibrotic microenvironments. Critically, it tackles translational complexity by incorporating the heterogeneity of lesions uncovered through single-cell and spatial transcriptomics, and by assessing the experimental models necessary to determine causal relevance. Additionally, it addresses the paradox of targeting ZEB1 therapeutically, considering its physiological function in endometrial regeneration and implantation. Understanding the oestrogen-ZEB1-TGF-β axis is critical for developing mechanism-based precision interventions for endometriosis.
(© 2026. The Author(s), under exclusive licence to Society for Reproductive Investigation.)
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
Σχόλια: Erratum in: Reprod Sci. 2026 Sep 16. doi: 10.1007/s43032-026-02212-6.. (PMID: 42747717)
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Contributed Indexing: Keywords: Endometriosis; Epithelial-mesenchymal transition (EMT); Fibrosis; Non-coding RNAs; Oestrogen signalling; Progesterone resistance; TGF-β signalling; ZEB1
Substance Nomenclature: 0 (Zinc Finger E-box-Binding Homeobox 1)
0 (ZEB1 protein, human)
0 (MicroRNAs)
SCR Disease Name: Progesterone Resistance
Entry Date(s): Date Created: 20260910 Date Completed: 20261008 Latest Revision: 20261008
Update Code: 20261008
DOI: 10.1007/s43032-026-02181-w
PMID: 42717122
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1933-7205
DOI:10.1007/s43032-026-02181-w