Trial reportJournal of molecular medicine (Berlin, Germany)2017
Fenretinide differentially modulates the levels of long- and very long-chain ceramides by downregulating Cers5 enzyme: evidence from bench to bedside.
Trial report in Journal of molecular medicine (Berlin, Germany), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Vitamin A and beta (β)-carotene supplementation for cystic fibrosis.The Cochrane database of systematic reviews · 2018Pooled it
- Efficacy and safety of LAU-7b in a Phase 2 trial in adults with cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2025Trial
- Ceramide-Driven Mechanisms in Pulmonary Fibrosis.Metabolites · 2026Review
- Review
- Cross-talk between CFTR and sphingolipids in cystic fibrosis.FEBS open bio · 2023Review
- Regulatory T cell enhancement in adults with cystic fibrosis receiving Elexacaftor/Tezacaftor/Ivacaftor therapy.Frontiers in immunology · 2023Article
- Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.Journal of medicinal chemistry · 2022Review
- Lipid-driven CFTR clustering is impaired in cystic fibrosis and restored by corrector drugs.Journal of cell science · 2022Article
- Treatment With LAU-7b Complements CFTR Modulator Therapy by Improving Lung Physiology and Normalizing Lipid Imbalance Associated With CF Lung Disease.Frontiers in pharmacology · 2022Article
- Sphingomyelinase decreases transepithelial anion secretion in airway epithelial cells in part by inhibiting CFTR-mediated apical conductance.Physiological reports · 2021Article
- CFTR Correctors and Antioxidants Partially Normalize Lipid Imbalance but not Abnormal Basal Inflammatory Cytokine Profile in CF Bronchial Epithelial Cells.Frontiers in physiology · 2021Article
- The role of essential fatty acids in cystic fibrosis and normalizing effect of fenretinide.Cellular and molecular life sciences : CMLS · 2020Review
- Proteomics and Metabolomics for Cystic Fibrosis Research.International journal of molecular sciences · 2020Review
- Article
- The bidirectional relationship between CFTR and lipids.Communications biology · 2020Review
- Efficacy of Optimized Treatment Protocol Using LAU-7b Formulation against Ovalbumin (OVA) and House Dust Mite (HDM) -Induced Allergic Asthma in Atopic Hyperresponsive A/J Mice.Pharmaceutical research · 2020Article
- Agonists that stimulate secretion promote the recruitment of CFTR into membrane lipid microdomains.The Journal of general physiology · 2019Article
- Ceramide and Regulation of Vascular Tone.International journal of molecular sciences · 2019Review
- Cystic fibrosis: the conductance regulator, ceramides, and possible treatments.Journal of molecular medicine (Berlin, Germany) · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystic fibrosis is the most common genetic disease, in which symptoms may be alleviated but not fully eliminated. Ceramides have long been implicated in the inflammatory etiology of cystic fibrosis, with contradicting reports with regards to their role. Recently, significant biological and biophysical differences have been observed between long- and very long-chain ceramides. This work reveals that long-chain ceramides are upregulated whereas very long-chain ceramides are downregulated in cell lines, mouse animal model, and patients with cystic fibrosis, compared with their controls. Treatment with fenretinide decreases the levels of long-chain ceramides and increases the levels of very long-chain ceramides. Our results show that restoration of cystic fibrosis conductance regulator (CFTR) expression is associated with normalization of aberrant levels of specific ceramides. This demonstrates for the first time a correlation between CFTR protein expression and regulation of specific ceramide levels. Furthermore, using cystic fibrosis lung epithelial cell lines, we demonstrate that this effect can be attributed to the transcriptional downregulation of ceramide synthase 5 (Cers5) enzyme. We also discovered a partial synergism between fenretinide and zinc (Zn KEY MESSAGES: Long- and very long-chain ceramides (LCCs and VLCCs) are biochemically distinct. LCCs are upregulated whereas VLCCs are downregulated in cystic fibrosis. Fenretinide downregulates the levels of LCCs and upregulates the levels of VLCCs. Fenretinide changes the balance of LCCs and VLCCs by downregulating Cers5 enzyme. Fenretinide and zinc ions cooperate in the modulation of ceramide levels.
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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.