Activated Platelets Induce Estrogen Receptor β Expression in Endometriotic Stromal Cells
Abstract
Background/Aims: Endometriosis is viewed first and foremost as an estrogen-dependent disease, featuring not only excessive estrogen production but also aberrant expression of estrogen receptors (ERs), particularly ERβ, that mediate the estrogen action. ERβ is the predominant ER in mediating estrogen action in endometriosis, and estrogen plays a vital role in the development of endometriosis; thus, ERβ is viewed as a strong candidate for therapeutic targeting. Given our recent finding that platelets aggregate in endometriotic lesions, we sought to investigate whether activated platelets can upregulate ERβ. Methods: Using primary endometriotic stromal cells derived from patients with ovarian endometriomas and platelets harvested from healthy donors, we performed real-time RT-PCR analysis of mRNA abundance (n = 8) and Western blot analysis of protein expression (n = 8) of ERα and ERβ when co-cultured with phosphate-buffered saline, platelets, thrombin alone, and platelets plus thrombin for 48 h. Results: Treatment of endometriotic stromal cells with activated platelets resulted in the upregulation of ERβ gene and protein expression. Conclusion: In the presence of aggregated and thus activated platelets in endometriotic lesions, ERβ, but not ERα, is upregulated in endometriotic stromal cells. Our result suggests that the use of antiplatelet therapy may have potential in the treatment of endometriosis.
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ERβ expression can also be upregulated by activated platelets.
“we have shown previously that ERβ expression can also be upregulated by activated platelets73.”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [73]
The purity of primary endometriotic stromal cells was confirmed by positive vimentin and negative CK7 staining after the third passage, and contamination with ovarian granulosa cells was ruled out by negative follicle stimulating hormone receptor staining.
“The vimentin staining was positive and the CK7 staining was negative after the third passage. To rule out the possibility of contamination with ovarian granulosa cells, we also stained the primary cells with follicle stimulating hormone receptor (Abcam, Cambridge, UK), a specific marker for granulosa cells118. The staining was found to be negative, as we previously reported119.”
From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [119]
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References 36 · Cited by 38
- Authors
- Zhang, Q., Ding, D., Liu, X., & Guo, S.-W.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- Venue
- Gynecologic and Obstetric Investigation
- Publisher
- S. Karger AG
- Published
- 2015
- Volume
- 80
- Issue
- 3
- Pages
- 187-192
- ISSN
- 0378-7346 (ISSN-L)
- 1423-002X
- OpenAlex
- W2048344171
- Cited by
- 38
- References
- 36
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 8 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 8
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gynecologic and Obstetric Investigation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Keywords
- endometriosis, estrogen receptor beta, estrogen receptor alpha, platelet activation, endometriotic stromal cells, platelet aggregation, thrombin, antiplatelet therapy, endometrioma, estrogen signaling
- MeSH terms
- Blood Platelets, Endometriosis, Endometrium, Female, Humans, Immunohistochemistry, Middle Aged, Blotting, Western, Platelet Activation, Stromal Cells, Estrogen Receptor alpha, Estrogen Receptor beta, Real-Time Polymerase Chain Reaction
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