ArticleEndocrinology and metabolism (Seoul, Korea)2024
In Vitro Investigation of HIF-1α as a Therapeutic Target for Thyroid-Associated Ophthalmopathy.
Article in Endocrinology and metabolism (Seoul, Korea), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Elevated blood viscosity in thyroid-associated ophthalmopathy and its association with thyroid-stimulating immunoglobulin levels.Scientific reports · 2026Article
- Metabolic reprogramming of Th17/Treg imbalance in autoimmune thyroid diseases.Cell communication and signaling : CCS · 2026Review
- Hypoxia-Inducible Factor 1-α in Autoimmune Diseases-Insights from the Paradigm of Hashimoto's Thyroiditis: A Narrative Review.Medical sciences (Basel, Switzerland) · 2026Review
- Integrative transcriptomic profiling and machine learning reveal hypoxia-associated molecular signatures for precision diagnosis in thyroid eye disease.Human genomics · 2025Article
- Unravelling the pathogenic mechanisms in Graves' orbitopathy.European thyroid journal · 2025Review
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Authors and funding
10 authors.
Funding
Abstract
backgruoundThyroid-associated ophthalmopathy (TAO) involves tissue expansion and inflammation, potentially causing a hypoxic microenvironment. Hypoxia-inducible factor (HIF)-1α is crucial in fibrosis and adipogenesis, which are observed in TAO progression. We investigated the effects of hypoxia on orbital fibroblasts (OFs) in TAO, focusing on the role of HIF-1α in TAO progression.
methodsOFs were isolated from TAO and non-TAO patients (as controls). In addition to HIF-1α, adipogenic differentiation markers including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (CEBP) were measured by Western blot, and phenotype changes were evaluated by Oil Red O staining under both normoxia and hypoxia. To elucidate the effect of HIF-1α inhibition, protein expression changes after HIF-1α inhibitor treatment were evaluated under normoxia and hypoxia.
resultsTAO OFs exhibited significantly higher HIF-1α expression than non-TAO OFs, and the difference was more distinct under hypoxia than under normoxia. Oil Red O staining showed that adipogenic differentiation of TAO OFs was prominent under hypoxia. Hypoxic conditions increased the expression of adipogenic markers, namely PPARγ and CEBP, as well as HIF-1α in TAO OFs. Interleukin 6 levels also increased in response to hypoxia. The effect of hypoxia on adipogenesis was reduced at the protein level after HIF-1α inhibitor treatment, and this inhibitory effect was sustained even with IGF-1 stimulation in addition to hypoxia.
conclusionHypoxia induces tissue remodeling in TAO by stimulating adipogenesis through HIF-1α activation. These data could provide insights into new treatment strategies and the mechanisms of adipose tissue remodeling in TAO.
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