ArticleInternational journal of molecular sciences2021
miR-199a Downregulation as a Driver of the NOX4/HIF-1α/VEGF-A Pathway in Thyroid and Orbital Adipose Tissues from Graves' Patients.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Pooled it
- Serum Biomarkers Linked to Disease Activity, Severity, and Methylprednisolone Response in Graves' Orbitopathy: A Proteomic Study.Investigative ophthalmology & visual science · 2025Article
- Unravelling the pathogenic mechanisms in Graves' orbitopathy.European thyroid journal · 2025Review
- Investigation of the molecular mechanism of Xiaoluo Wan in thyroid-associated ophthalmopathy: network analysis and in vivo study.Hereditas · 2025Article
- miR-125b differentially impacts mineralization in dexamethasone and calcium-treated human mesenchymal stem cells.Molecular therapy. Nucleic acids · 2025Article
- The Relevance and Potential Role of Orbital Fat in Inflammatory Orbital Diseases: Implications for Diagnosis and Treatment.Ophthalmology and therapy · 2025Review
- Network pharmacology and experiments verify the effect of triptolide on extraocular muscle fibrosis.PloS one · 2025Article
- A method for isolating and culturing ectopic epithelial and stromal cells to study human adenomyosis.Archives of gynecology and obstetrics · 2024Article
- Non-coding RNA-mediated epigenetic alterations in Grave's ophthalmopathy: A scoping systematic review.Non-coding RNA research · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Graves' disease (GD) is an autoimmune thyroiditis often associated with Graves' orbitopathy (GO). GD thyroid and GO orbital fat share high oxidative stress (OS) and hypervascularization. We investigated the metabolic pathways leading to OS and angiogenesis, aiming to further decipher the link between local and systemic GD manifestations. Plasma and thyroid samples were obtained from patients operated on for multinodular goiters (controls) or GD. Orbital fats were from GO or control patients. The NADPH-oxidase-4 (NOX4)/HIF-1α/VEGF-A signaling pathway was investigated by Western blotting and immunostaining. miR-199a family expression was evaluated following quantitative real-time PCR and/or in situ hybridization. In GD thyroids and GO orbital fats, NOX4 was upregulated and correlated with HIF-1α stabilization and VEGF-A overexpression. The biotin assay identified NOX4, HIF-1α and VEGF-A as direct targets of miR-199a-5p in cultured thyrocytes. Interestingly, GD thyroids, GD plasmas and GO orbital fats showed a downregulation of miR-199a-3p/-5p. Our results also highlighted an activation of STAT-3 signaling in GD thyroids and GO orbital fats, a transcription factor known to negatively regulate miR-199a expression. We identified NOX4/HIF-1α/VEGF-A as critical actors in GD and GO. STAT-3-dependent regulation of miR-199a is proposed as a common driver leading to these events in GD thyroids and GO orbital fats.
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