ArticleFree radical biology & medicine2017
TRPV4 activation of endothelial nitric oxide synthase resists nonalcoholic fatty liver disease by blocking CYP2E1-mediated redox toxicity.
Article in Free radical biology & medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- The effects of high-intensity interval training and Iranian propolis extract on serum levels of TRPV4 and CYP2E1 proteins in patients with nonalcoholic fatty liver.La Tunisie medicale · 2024Trial
- Urea cycle dysregulation and arginine pathways in the pathogenesis of NAFLD and NASH (Review).International journal of molecular medicine · 2026Review
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- Calcium imbalance drives organelle network collapse and immune remodeling: novel pathogenic mechanisms in MASLD progression.Frontiers in immunology · 2026Review
- A QUARTER CENTURY OF CALCIUM-PERMEABLE ION CHANNEL, TRPV4: PERSPECTIVES ON EXPRESSION AND FUNCTION IN ENDOTHELIAL CELLS-TIME TO TRANSLATE.Transactions of the American Clinical and Climatological Association · 2025Review
- Resveratrol Modulates Diabetes-Induced Neuropathic Pain, Apoptosis, and Oxidative Neurotoxicity in Mice Through TRPV4 Channel Inhibition.Molecular neurobiology · 2024Article
- Hepatic TRPC3 loss contributes to chronic alcohol consumption-induced hepatic steatosis and liver injury in mice.Life metabolism · 2024Article
- Role of TRP Channels in Metabolism-Related Diseases.International journal of molecular sciences · 2024Review
- Mechanosensing in Metabolism.Comprehensive Physiology · 2023Review
- Hepatic NLRP3-Derived Hsp70 Binding to TLR4 Mediates MASLD to MASH Progression upon Inhibition of PP2A by Harmful Algal Bloom Toxin Microcystin, a Second Hit.International journal of molecular sciences · 2023Article
- TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases.Signal transduction and targeted therapy · 2023Review
- Inhibition of TRPV4 remodels single cell polarity and suppresses the metastasis of hepatocellular carcinoma.Cell death & disease · 2023Article
- A time differentiated dietary intervention effect on the biomarkers of exposure to pyrethroids and neonicotinoids pesticides.iScience · 2023Article
- Expression and functions of transient receptor potential channels in liver diseases.Acta pharmaceutica Sinica. B · 2023Review
- Role of CaInternational journal of molecular medicine · 2022Review
- Article
- Xenobiotic-Induced Aggravation of Metabolic-Associated Fatty Liver Disease.International journal of molecular sciences · 2022Review
- Diverse Roles of TRPV4 in Macrophages: A Need for Unbiased Profiling.Frontiers in immunology · 2021Review
- Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Cutaneous sensory nerve-mediated microvascular vasodilation in normotensive and prehypertensive non-Hispanic Blacks and Whites.Physiological reports · 2020Article
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12 authors.
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Abstract
NAFLD is a clinically progressive disease with steatosis, inflammation, endothelial dysfunction and fibrosis being the stages where clinical intervention becomes necessary. Lack of early biomarkers and absence of a FDA approved drug obstructs efforts for effective treatment. NAFLD progression is strongly linked to a balance between liver injury, tissue regeneration and the functioning of endogenous defense mechanisms. The failure of the defense pathways to resist the tissue damage arising from redox stress, one of the "multiple hits" in disease progression, give rise to heightened inflammation and occasional fibrosis. We introduce an endogenous defense mechanism in the liver that is mediated by TRPV4, a transient receptor potential calcium-permeable ion channel that responds to the cytotoxic liver environment and negatively regulates CYP2E1, a cytochrome p450 enzyme. Using Trpv4-/- mice and cultured primary cells, we show that TRPV4 is activated both by damage associated molecular pattern HMGB1 and collagen in diseased Kupffer cells that in turn activate the endothelial NOS (NOS3) to release nitric oxide (NO). The diffusible NO acts in a paracrine fashion in neighboring hepatocytes to deactivate the redox toxicity induced by CYP2E1. We also find that CYP2E1-mediated TRPV4 repression in late stages causes an unrestricted progression of disease. Thus, TRPV4 functions as a sensor of cell stress in the diseased fatty liver and constitutes an endogenous defense molecule, a novel concept with potential for therapeutic approaches against NAFLD, perhaps also against hepatic drug toxicity in general.
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