ArticleThe American journal of pathology2016
Interferon-γ-Induced Unfolded Protein Response in Conjunctival Goblet Cells as a Cause of Mucin Deficiency in Sjögren Syndrome.
Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 102 citations in OpenAlex.
- Randomized Controlled Crossover Trial Comparing the Impact of Sham or Intranasal Tear Neurostimulation on Conjunctival Goblet Cell Degranulation.American journal of ophthalmology · 2017Trial
- Pathological mechanisms of Sjögren's disease-related dry eye: from multiglandular dysfunction to ocular surface inflammation.International ophthalmology · 2026Review
- Depression induces ocular surface inflammation and dry eye-like changes in mice.International journal of ophthalmology · 2026Article
- Dry eye-related tear biomarkers MMP-2, MMP-13, and IFN-γ: potential predictors of Type III acute acquired concomitant esotropia.European journal of medical research · 2025Article
- IFNγ augments TKI efficacy by alleviating protein unfolding stress to promote GSDME-mediated pyroptosis in hepatocellular carcinoma.Cell death & disease · 2025Article
- Emerging Age-Specific Therapeutic Approaches for Dry Eye Disease.Journal of clinical medicine · 2025Review
- Endoplasmic reticulum stress in the salivary glands of patients with primary Sjögren's syndrome, associated Sjögren's syndrome, and non-Sjögren's sicca syndrome: a comparative analysis and the influence of chloroquine.Advances in rheumatology (London, England) · 2025Article
- Endoplasmic Reticulum Stress Induces ROS Production and Activates NLRP3 Inflammasome Via the PERK-CHOP Signaling Pathway in Dry Eye Disease.Investigative ophthalmology & visual science · 2024Article
- Purinergic agonists increase [CaAmerican journal of physiology. Cell physiology · 2024Article
- Immune-Mediated Ocular Surface Disease in Diabetes Mellitus-Clinical Perspectives and Treatment: A Narrative Review.Biomedicines · 2024Review
- Ectoine Enhances Mucin Production Via Restoring IL-13/IFN-γ Balance in a Murine Dry Eye Model.Investigative ophthalmology & visual science · 2024Article
- Astaxanthin activated the SLC7A11/GPX4 pathway to inhibit ferroptosis and enhance autophagy, ameliorating dry eye disease.Frontiers in pharmacology · 2024Article
- Conditional deletion of CD25 in the corneal epithelium reveals sex differences in barrier disruption.The ocular surface · 2023Article
- Endoplasmic reticulum stress: molecular mechanism and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype.Investigative ophthalmology & visual science · 2023Article
- Effect of Lutein on Ocular Goblet Cell, IFN-γ, and IL-17 Concentration in Dry Eye-Induced Mice Model.Cureus · 2023Article
- Interferon-γ elicits the ocular surface pathology mimicking dry eye through direct modulation of resident corneal cells.Cell death discovery · 2023Article
- Induction of Innate Inflammatory Pathways in the Corneal Epithelium in the Desiccating Stress Dry Eye Model.Investigative ophthalmology & visual science · 2023Article
- Heterochronic Parabiosis Causes Dacryoadenitis in Young Lacrimal Glands.International journal of molecular sciences · 2023Article
- Dynasore Protects Corneal Epithelial Cells Subjected to Hyperosmolar Stress in an In Vitro Model of Dry Eye Epitheliopathy.International journal of molecular sciences · 2023Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Goblet cells (GCs) are specialized secretory cells that produce mucins and a variety of other proteins. Significant conjunctival GC loss occurs in both experimental dry eye models and patients with keratoconjunctivitis sicca due to the induction of interferon (IFN)-γ. With the use of a primary murine culture model, we found that GCs are highly sensitive to IFN-γ with significantly reduced proliferation and altered structure with low concentrations. GC cultures treated with IFN-γ have increased gene expression of Muc2 and Muc5AC but do not express these mucin glycoproteins. We hypothesized that IFN-γ induces endoplasmic reticulum stress and the unfolded protein response (UPR) in GCs. Cultures treated with IFN-γ increased expression of UPR-associated genes and proteins. Increased GRP78 and sXBP1 expression was found in experimental dry eye and Sjögren syndrome models and was GC specific. Increased GRP78 was also found in the conjunctiva of patients with Sjögren syndrome at the gene and protein levels. Treatment with dexamethasone inhibited expression of UPR-associated genes and increased mucin production. These results indicate that induction of UPR by IFN-γ is an important cause of GC-associated mucin deficiency observed in aqueous-deficient dry eye. Therapies to block the effects of IFN-γ on the metabolically active endoplasmic reticulum in these cells might enhance synthesis and secretion of the protective GC mucins on the ocular surface.
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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.