ArticleScientific reports2017
Tricyclic Antidepressants Promote Ceramide Accumulation to Regulate Collagen Production in Human Hepatic Stellate 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 20 papers.
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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
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Effects of Diet and Exercise on Mitochondrial Health in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Role of Ceramides.Nutrients · 2025Review
- Resolving fibrosis by stimulating HSC-dependent extracellular matrix degradation.Science translational medicine · 2025Article
- Screening the human druggable genome identifies ABHD17B as an anti-fibrotic target in hepatic stellate cells.Nature communications · 2025Article
- Tension-induced organelle stress: an emerging target in fibrosis.Trends in pharmacological sciences · 2025Review
- Baccharis articulata aqueous extract exerts in vitro antifibrotic effect in hepatic stellate cells by attenuating collagen deposition and TGF-ß1 protein expression.EXCLI journal · 2025Article
- Depressive symptom as a risk factor for cirrhosis in patients with primary biliary cholangitis: Analysis based on Lasso-logistic regression and decision tree models.Brain and behavior · 2024Article
- Article
- Scoping review and interpretation of myofascial pain/fibromyalgia syndrome: An attempt to assemble a medical puzzle.PloS one · 2022Article
- Targeting acid ceramidase ameliorates fibrosis in mouse models of non-alcoholic steatohepatitis.Frontiers in medicine · 2022Article
- Imipramine impedes glioma progression by inhibiting YAP as a Hippo pathway independent manner and synergizes with temozolomide.Journal of cellular and molecular medicine · 2021Article
- Roles of Ceramides in Non-Alcoholic Fatty Liver Disease.Journal of clinical medicine · 2021Review
- Targeting acid ceramidase inhibits YAP/TAZ signaling to reduce fibrosis in mice.Science translational medicine · 2020Article
- Elusive Roles of the Different Ceramidases in Human Health, Pathophysiology, and Tissue Regeneration.Cells · 2020Review
- Biomarker discovery for chronic liver diseases by multi-omics - a preclinical case study.Scientific reports · 2020Article
- Hepatic stellate cell activation: A source for bioactive lipids.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Article
- Amitriptyline attenuates bleomycin-induced pulmonary fibrosis: modulation of the expression of NF-κβ, iNOS, and Nrf2.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- Transcriptional regulation of Hepatic Stellate Cell activation in NASH.Scientific reports · 2019Article
- Role of sphingolipids in senescence: implication in aging and age-related diseases.The Journal of clinical investigation · 2018Review
- Tricyclic antidepressant use and the risk of fibrosis progression in hepatitis C-infected persons: Results from ERCHIVES.Journal of viral hepatitis · 2018Article
- The Protective Effects and Mechanism of Doxepin on Radiation-Induced Lung Injury in Rats.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
Activation of hepatic stellate cells (HSCs) in response to injury is a key step in hepatic fibrosis, and is characterized by trans-differentiation of quiescent HSCs to HSC myofibroblasts, which secrete extracellular matrix proteins responsible for the fibrotic scar. There are currently no therapies to directly inhibit hepatic fibrosis. We developed a small molecule screen to identify compounds that inactivate human HSC myofibroblasts through the quantification of lipid droplets. We screened 1600 compounds and identified 21 small molecules that induce HSC inactivation. Four hits were tricyclic antidepressants (TCAs), and they repressed expression of pro-fibrotic factors Alpha-Actin-2 (ACTA2) and Alpha-1 Type I Collagen (COL1A1) in HSCs. RNA sequencing implicated the sphingolipid pathway as a target of the TCAs. Indeed, TCA treatment of HSCs promoted accumulation of ceramide through inhibition of acid ceramidase (aCDase). Depletion of aCDase also promoted accumulation of ceramide and was associated with reduced COL1A1 expression. Treatment with B13, an inhibitor of aCDase, reproduced the antifibrotic phenotype as did the addition of exogenous ceramide. Our results show that detection of lipid droplets provides a robust readout to screen for regulators of hepatic fibrosis and have identified a novel antifibrotic role for ceramide.
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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.