ArticleCell death & disease2014
Activation of HIF-1α (hypoxia inducible factor-1α) prevents dry eye-induced acinar cell death in the lacrimal gland.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- Autophagy modulation in animal models of corneal diseases: a systematic review.Molecular and cellular biochemistry · 2020Pooled it
- Corneal lymphangiogenesis as a potential target in dry eye disease - a systematic review.Survey of ophthalmologyPooled it
- Trial
- Pathophysiology of the gut-eye axis in a Sjögren's disease-like dry eye mouse model: An exploratory evaluation of dietary heat-treated Enterococcus faecalis FK-23.Experimental physiology · 2026Article
- Inhibition of SGK1 Alleviates Apoptosis and Oxidative Stress in Dry Eye Disease by Activating FoxO3a-Mediated Autophagy.Investigative ophthalmology & visual science · 2026Article
- Immune Regulatory Role of Parasympathetic Nervous System in Murine Corneal Allografts via Inhibition of Dendritic Cell Activation and T Cell Polarization.Investigative ophthalmology & visual science · 2026Article
- Hypoxia-Inducible Factor 1-α in Autoimmune Diseases-Insights from the Paradigm of Hashimoto's Thyroiditis: A Narrative Review.Medical sciences (Basel, Switzerland) · 2026Review
- Autophagy is required for the development and functionality of lacrimal gland-like organoids.Stem cell reports · 2026Article
- FGF10 Protects the Corneal Epithelium From Dry Eye-Induced Oxidative and ER Stress Via Upregulation of SLC7A11.Investigative ophthalmology & visual science · 2025Article
- Rebamipide Enhances Pathogen Defense and Mitigates Inflammation in a Particulate Matter-Induced Ocular Surface Inflammation Rat Model.International journal of molecular sciences · 2025Article
- The role of hypoxic microenvironment in autoimmune diseases.Frontiers in immunology · 2024Review
- Purple Corn Extract Improves Dry Eye Symptoms in Models Induced by Desiccating Stress and Extraorbital Lacrimal Gland Excision.Nutrients · 2023Article
- Purple Sweet Potato Powder Containing Anthocyanin Mitigates High-Fat-Diet-Induced Dry Eye Disease.International journal of molecular sciences · 2023Article
- Tear proteomics in dry eye disease.Indian journal of ophthalmology · 2023Review
- Autophagy in dry eye disease: Therapeutic implications of autophagy modulators on the ocular surface.Indian journal of ophthalmology · 2023Review
- Dynasore Protects Corneal Epithelial Cells Subjected to Hyperosmolar Stress in an In Vitro Model of Dry Eye Epitheliopathy.International journal of molecular sciences · 2023Article
- Impact of Lacrimal Gland Extraction on the Contralateral Eye in an Animal Model for Dry Eye Disease.Korean journal of ophthalmology : KJO · 2022Article
- Exosomes and autophagy in ocular surface and retinal diseases: new insights into pathophysiology and treatment.Stem cell research & therapy · 2022Review
- Review
- Obstructive Sleep Apnea Affects Lacrimal Gland Function.Investigative ophthalmology & visual science · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pathogenesis of immune-mediated lacrimal gland (LG) dysfunction in Sjögren's syndrome has been thoroughly studied. However, the majority of dry eye (DE) is not related to Sjögren type, and its pathophysiology remains unclear. The purpose of this study was to determine and investigate the protective mechanisms against DE stress in mice. DE induced prominent blood vessel loss without apoptosis or necrosis in the LG. Autophagic vacuoles, distressed mitochondria, and stressed endoplasmic reticulum were observed via electron microscopy. Immunoblotting confirmed the increase in autophagic markers. Glycolytic activities were enhanced with increasing levels of succinate and malate that, in turn, activated hypoxia-inducible factor (HIF)-1α. Interestingly, the areas of stable HIF-1α expression overlapped with COX-2 and MMP-9 upregulation in LGs of DE-induced mice. We generated HIF-1α conditional knockout (CKO) mice in which HIF-1α expression was lost in the LG. Surprisingly, normal LG polarities and morphologies were completely lost with DE induction, and tremendous acinar cell apoptosis was observed. Similar to Sjögren's syndrome, CD3(+) and CD11b(+) cells infiltrated HIF-1α CKO LGs. Our results show that DE induced the expression of HIF-1α that activated autophagy signals to prevent further acinar cell damage and to maintain normal LG function.
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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.