NR4A1 is Involved in Fibrogenesis in Ovarian Endometriosis
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⤵ 19 in-corpus citations
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Phosphorylated NR4A1 levels are elevated in ovarian endometriosis, and NR4A1 inhibition promotes fibrosis, suggesting it regulates fibrogenesis and is a potential therapeutic target.
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Abstract
BACKGROUND/AIMS: Excess fibrosis may lead to chronic pain, scarring, and infertility as endometriosis develops and progresses. The pathogenesis of endometriosis has been linked to transforming growth factor-β (TGF-β), the most potent promoter of fibrosis.
METHODS: Levels of NR4A1 and P-NR4A1 protein in human endometrial and endometriotic tissue were assessed by western blotting and immunohistochemistry. The expression levels of fibrotic markers in stromal cells were evaluated by real-time PCR. The degree of fibrosis in mouse endometriotic lesions was detected by Masson trichrome and Sirius red staining.
RESULTS: The level of phosphorylated-NR4A1 was higher in ovarian endometriotic tissue than in normal endometrium, and long-term TGF-β1 stimulation phosphorylated NR4A1 in an AKT-dependent manner and then promoted the expression of fibrotic markers. Furthermore, inhibition of NR4A1 in stromal cells increased the TGF-β1-dependent elevated expression of fibrotic markers, and loss of NR4A1 stimulated fibrogenesis in mice with endometriosis. Additionally, Cytosporone B (Csn-B), an NR4A1 agonist, effectively decreased the TGF-β1-dependent elevated expression of fibrotic markers in vitro and significantly inhibited fibrogenesis in vivo.
CONCLUSION: NR4A1 can regulate fibrosis in endometriosis and may serve as a new target for the treatment of endometriosis.
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Cited by (20)
- A transcriptomics-based computational drug repurposing pipeline identifies simvastatin and primaquine as therapeutics for endometriosis 2026
- Characteristics of menstrual blood-derived stem cells from women with endometriosis: A systematic review 2026
- Marker-independent imaging reveals a correlation of fibrotic and epigenetic alterations in endometriosis 2025
- Pathophysiology of Endometriosis: Insights from Immunohistochemical Analysis of Ectopic and Eutopic Tissues 2025
- THBS1 identificated as an endometriosis biomarker through evidence from single-cell and bulk transcriptomic profiling 2025
- Expression Profiling of Coding and Noncoding RNAs in the Endometrium of Patients with Endometriosis 2024
- The role of fibrosis in endometriosis: a systematic review 2024
- Experimental modeling, prevention, and treatment of endometriosis-associated adhesion formation in NIH/3T3 fibroblast cell line using bovhyaluronidase azoximer (in vitro) 2024
- PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis 2023
- Endometriosis: Cellular and Molecular Mechanisms Leading to Fibrosis 2022
- DROSHA rs10719 and DICER1 rs3742330 polymorphisms in endometriosis and different diseases: Case-control and review studies 2021
- Target identification and drug discovery by data-driven hypothesis and experimental validation in ovarian endometriosis 2021
- Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis 2021
- A cellular and molecular portrait of endometriosis subtypes 2021
- Bis-Indole-Derived Nuclear Receptor 4A1 (NR4A1, Nur77) Ligands as Inhibitors of Endometriosis 2020
- Towards an understanding of the molecular mechanisms of endometriosis-associated symptoms (Review) 2020
- Erastin induces ferroptosis via ferroportin-mediated iron accumulation in endometriosis 2020
- A progestin isn't a progestin: dienogest for endometriosis as a blueprint for future research - Review as a contribution for discussion 2020
- Cellular Components Contributing to Fibrosis in Endometriosis: A Literature Review 2019
- Anti-inflammatory cytokines in endometriosis 2019
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- europepmc
- last seen: 2026-10-15T06:08:49.021275+00:00
- openalex
- last seen: 2026-06-04T00:00:01.174412+00:00
- pubmed
- last seen: 2026-10-08T21:21:58.428726+00:00
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