ArticleEndocrinology2019
HIF2A-LOX Pathway Promotes Fibrotic Tissue Remodeling in Thyroid-Associated Orbitopathy.
Article in Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 85 citations in OpenAlex.
- EBF2 variant identified in a patient with atypical partial lipodystrophy causes adipose fibrosis and dysfunction.The Journal of clinical investigation · 2026Article
- Orbital decompression with intraorbital corticosteroid injection during the active phase of thyroid eye disease: outcomes in a real-world cohort.Frontiers in ophthalmology · 2026Article
- Macrophage plasticity in thyroid eye disease: dual effects of inflammation and fibrosis.Frontiers in immunology · 2026Review
- Pan-Cancer Analysis Reveals AEBP1-Collagen Co-Expression and Its Potential Role in CAF-Mediated Tumor Stiffness.International journal of molecular sciences · 2025Article
- 2'-O-Galloylhyperin Prevents Tissue Remodeling in Thyroid Eye Disease: Prospects as a Thyrotropin Receptor Antagonist.The Journal of clinical endocrinology and metabolism · 2025Article
- Fatty Acid Metabolism Regulators Have Pivotal Roles in the Pathogenesis of Ovarian Carcinoma.International journal of molecular sciences · 2025Article
- Recent advances in the study of the correlation between obstructive sleep apnea and thyroid-disorders.Sleep & breathing = Schlaf & Atmung · 2025Review
- Effects of linsitinib on M22 and IGF:1-treated 3D spheroids of human orbital fibroblasts.Scientific reports · 2025Article
- Inhibition of mTOR differently modulates planar and subepithelial fibrogenesis in human conjunctival fibroblasts.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Article
- Article
- TGF-β effects on adipogenesis of 3T3-L1 cells differ in 2D and 3D cell culture conditions.FEBS open bio · 2024Article
- Role of Lysyl Oxidase-Like Protein 3 in the Pathogenesis of Graves' Orbitopathy in Orbital Fibroblasts.Investigative ophthalmology & visual science · 2024Article
- Unexpected and Synergistical Effects of All-Trans Retinoic Acid and TGF-β2 on Biological Aspects of 2D and 3D Cultured ARPE19 Cells.Biomedicines · 2024Article
- Review
- Lysophosphatidic Acid Modulates TGF-β2-Induced Biological Phenotype in Human Conjunctival Fibroblasts.Life (Basel, Switzerland) · 2024Article
- TGF-β Isoforms and Local Environments Greatly Modulate Biological Nature of Human Retinal Pigment Epithelium Cells.Bioengineering (Basel, Switzerland) · 2024Article
- Modulation of Epithelial-Mesenchymal Transition Is a Possible Underlying Mechanism for Inducing Chemoresistance in MIA PaCa-2 Cells against Gemcitabine and Paclitaxel.Biomedicines · 2024Article
- Significant and Various Effects of ML329-Induced MITF Suppression in the Melanoma Cell Line.Cancers · 2024Article
- Lipid Metabolism Regulators Are the Possible Determinant for Characteristics of Myopic Human Scleral Stroma Fibroblasts (HSSFs).International journal of molecular sciences · 2023Article
- Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Thyroid-associated orbitopathy (TAO) is a disfiguring periocular connective tissue disease associated with autoimmune thyroid disorders. It is a potentially blinding condition, for which no effective pharmacological treatment has been established. Despite a suggested role played by autoimmune thyrotropin receptor activation in the pathogenesis of TAO, the cellular and molecular events contributing to the fibrotic and inflammatory disease process of TAO are not fully defined. By developing a three-dimensional organoid culture of human orbital fibroblasts (OFs), we sought to determine the molecular mechanism underlying the fibrotic disease process of TAO. In this ex vivo model, we have demonstrated that hypoxia-inducible factor (HIF) 2α (HIF2A), but not its paralog HIF1A, accelerates extracellular matrix (ECM) deposition by inducing a collagen-cross-linking enzyme, lysyl oxidase (LOX). Inhibiting HIF2A and LOX with short hairpin RNA or small molecular antagonists effectively ameliorated fibrotic disease process within TAO organoids. Conversely, the overexpression of a constitutively active HIF2A in mouse OFs was sufficient to initiate LOX-dependent fibrotic tissue remodeling in OF organoids. Consistent with these findings, HIF2A and LOX were highly expressed in human TAO tissues paralleling excess ECM deposition. We propose that the HIF2A-LOX pathway can be a potential therapeutic target for the prevention and treatment of TAO.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.