ArticleScientific reports2017
Hyperosmolarity-induced AQP5 upregulation promotes inflammation and cell death via JNK1/2 Activation in human corneal epithelial cells.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
- Cadherin 1 negatively regulates SARS-CoV-2 infection in the olfactory epithelium.EMBO reports · 2026Article
- Pathological mechanisms of Sjögren's disease-related dry eye: from multiglandular dysfunction to ocular surface inflammation.International ophthalmology · 2026Review
- Therapeutic effects of Chelidonium majus on ocular surface ınflammation and tear film homeostasis in a benzalkonium chloride-ınduced rat model of dry eye disease.International ophthalmology · 2026Article
- T-LysYal for Managing Dry Eye Disease, the Advent of Supramolecular Aggregates in Ophthalmology: A Narrative Review.Journal of clinical medicine · 2026Review
- Hyperosmolarity-Induced Oxidative Stress Leads to Senescence in Human Corneal Epithelial Cells (HCEPC) via DNA Damage, Metabolic Disturbance and Mitophagy Decline.Antioxidants (Basel, Switzerland) · 2025Article
- Multicomponent Dietary Supplementation: Impact on Tear Secretion and Ocular Surface Inflammation in Dry Eye Syndrome Patients.Antioxidants (Basel, Switzerland) · 2025Article
- IL-1β-Mediated Immunometabolic Adaptation in Corneal Epithelial Cells.Journal of inflammation research · 2025Article
- Evaluation of the Performance of an Ocular Surface Modulator Containing ST-Lysyal Versus Hyaluronic Acid Eyedrops in Patients with Dry Eye Disease: A Pilot Study.Ophthalmology and therapy · 2025Article
- Discovery of a novel thiophene carboxamide analogue as a highly potent and selective sphingomyelin synthase 2 inhibitor for dry eye disease therapy.Acta pharmaceutica Sinica. B · 2025Article
- Establishment of human corneal epithelial organoids for ex vivo modelling dry eye disease.Cell proliferation · 2024Article
- From Gut to Eye: Exploring the Role of Microbiome Imbalance in Ocular Diseases.Journal of clinical medicine · 2024Review
- Reticulated Retinoic Acid Synthesis is Implicated in the Pathogenesis of Dry Eye in Aqp5 Deficiency Mice.Investigative ophthalmology & visual science · 2024Article
- Aquaporins in the Cornea.International journal of molecular sciences · 2024Review
- Targeting the Gut-Eye Axis: An Emerging Strategy to Face Ocular Diseases.International journal of molecular sciences · 2023Review
- Ion channels in dry eye disease.Indian journal of ophthalmology · 2023Review
- Role of aquaporins in corneal healing post chemical injury.Experimental eye research · 2023Review
- Article
- Aquaporins and Ion Channels as Dual Targets in the Design of Novel Glioblastoma Therapeutics to Limit Invasiveness.Cancers · 2023Review
- Aquaporin-5 Dynamic Regulation.International journal of molecular sciences · 2023Review
- IGFBP-3 Regulates Mitochondrial Hyperfusion and Metabolic Activity in Ocular Surface Epithelia during Hyperosmolar Stress.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tear film hyperosmolarity and anterior ocular inflammation are two clinical signs that may be indicative of dry eye disease (DED). This condition can cause pathological and functional changes to the anterior ocular surface tissues. A contributing factor may be dysfunctional aquaporin 5 (AQP5) water channels as they are the AQP subtype that expressed in the corneal epithelium and contribute to fluid efflux needed for corneal function. We determined if described hyperosmolarity-induced increases in proinflammatory cytokine expression and cell death are mediated through AQP5 upregulation and JNK1/2 MAPK signaling activation in both primary human corneal epithelial cells (HCECs), and in a HCEC line. Real time RT-PCR identified rises in IL-1β, IL-6, IL-8, TNF-α, caspase-1, and AQP5 mRNA levels upon step increases in osmolarity up to 550 mOsm. Western blot analysis and the TUNEL assay identified corresponding rises in AQP5 and p-JNK1/2 protein expression and cell death respectively. JNK1/2 inhibition with SP600125, or siRNA AQP5 gene silencing reduced hypertonic-induced rises in proinflammatory cytokine expression and cell death. Taken together, hypertonicity-induced AQP5 upregulation leads to increases in proinflammatory cytokine expression and cell death through JNK1/2 MAPK activation. These results suggest that drug targeting AQP5 upregulation may be a therapeutic option in DED management.
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