ArticleProceedings of the National Academy of Sciences of the United States of America2020
Extracellular vesicle-associated VEGF-C promotes lymphangiogenesis and immune cells infiltration in endometriosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 3 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 3 syntheses or guidelines pooled it, 76 citations in OpenAlex.
- The role of extracellular vesicles in endometriosis: A systematic review of pathogenesis, diagnostic biomarkers, and therapeutic potential.Molecular biology reports · 2026Pooled it
- WERF Endometriosis Phenome and Biobanking Harmonisation Project for Experimental Models in Endometriosis Research (EPHect-EM-Homologous): homologous rodent models.Molecular human reproduction · 2025Pooled it
- A promising future for endometriosis diagnosis and therapy: extracellular vesicles - a systematic review.Reproductive biology and endocrinology : RB&E · 2022Pooled it
- Endothelial cell heterogeneity drives angiogenesis in endometriosis: mechanisms and emerging organoid-based models.Apoptosis : an international journal on programmed cell death · 2026Review
- Do Oxidative Stress-Modified Exosomes Contribute to Infertility in Endometriosis?International journal of molecular sciences · 2026Review
- Molecular Insights Into Endometriosis for Early Detection and Therapeutic Targets.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Pro-EGCG suppresses endometriosis progression via regulating monocytic myeloid-derived suppressor cells.Chinese medicine · 2026Article
- Extracellular Vesicles in Endometriosis: A Comprehensive Review of Biological Insights and Methodological Challenges.International journal of molecular sciences · 2026Review
- Endometriosis at the Single-Cell Level: Molecular Insights and Implications for Assisted Reproduction Success.Biomolecules · 2026Review
- Molecular biology of targeting lymphangiogenesis in cancer: Therapeutic strategies and future promise.Fundamental research · 2026Review
- Traditional Chinese herbal medicines suppress endometriosis development through modulating macrophage-mediated immune responses in the peritoneal cavity.BioMedicine · 2026Article
- Endometriosis in para-aortic lymph nodes without any pelvic endometriosis: the first case report, sequencing analysis and literature review.BMC women's health · 2025Review
- Mouse Tumor Tissue-Derived Extracellular Vesicles Induce Angiogenesis Through VEGF Production From Macrophages.Journal of extracellular vesicles · 2025Article
- Does amide proton transfer-weighted MRI have diagnostic and differential value in ovarian cystic and predominantly cystic lesion?Abdominal radiology (New York) · 2025Article
- The role of the CXC chemokine family in endometriosis research and its therapeutic potential.Journal of molecular histology · 2025Review
- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- Endometriosis in Adolescence: A Narrative Review of the Psychological and Clinical Implications.Diagnostics (Basel, Switzerland) · 2025Review
- Identification of hub biomarkers and immune cell infiltrations participating in the pathogenesis of endometriosis.Scientific reports · 2025Article
- Intercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells.Molecular cancer · 2025Article
- Endometriosis: Future Biological Perspectives for Diagnosis and Treatment.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endometriosis is a highly prevalent gynecological disease with severe negative impacts on life quality and financial burden. Unfortunately, there is no cure for this disease, which highlights the need for further investigation about the pathophysiology of this disease to provide clues for developing novel therapeutic regimens. Herein, we identified that vascular endothelial growth factor (VEGF)-C, a potent lymphangiogenic factor, is up-regulated in endometriotic cells and contributes to increased lymphangiogenesis. Bioinformatic analysis and molecular biological characterization revealed that VEGF-C is negatively regulated by an orphan nuclear receptor, chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII). Further studies demonstrated that proinflammatory cytokines, via suppression of COUP-TFII level, induce VEGF-C overexpression. More importantly, we show that functional VEGF-C is transported by extracellular vesicles (EVs) to enhance the lymphangiogenic ability of lymphatic endothelial cells. Autotransplanted mouse model of endometriosis showed lenvatinib treatment abrogated the increased lymphatic vessels development in the endometriotic lesion, enlarged retroperitoneal lymph nodes, and immune cells infiltration, indicating that blocking VEGF-C signaling can reduce local chronic inflammation and concomitantly endometriosis development. Evaluation of EV-transmitted VEGF-C from patients' sera demonstrates it is a reliable noninvasive way for clinical diagnosis. Taken together, we identify the vicious cycle of inflammation, COUP-TFII, VEGF-C, and lymphangiogenesis in the endometriotic microenvironment, which opens up new horizons in understanding the pathophysiology of endometriosis. VEGF-C not only can serve as a diagnostic biomarker but also a molecular target for developing therapeutic regimens.
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