ArticlePloS one2013
Sympathetic nervous system catecholamines and neuropeptide Y neurotransmitters are upregulated in human NAFLD and modulate the fibrogenic function of hepatic stellate cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Blood pressure variability and its utility in acute disease and critical illness: a systematic review.BMC anesthesiology · 2025Pooled it
- NPY promotes macrophage polarization and hepatic fibrogenesis via PI3K/MAPK-dependent neuroimmune mechanisms.Cellular and molecular life sciences : CMLS · 2026Article
- Early Cardiotoxic Remodelling Precedes Hepatic Fibrosis and Increases Susceptibility to Lethal Arrhythmias in Wild-Type MASH Mice.Clinical and experimental pharmacology & physiology · 2026Article
- Hypothalamic Control of Liver Health and Disease: From Circuits to Pathophysiology and Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Catecholamines Activate a Tumour Progression Program in Differentiated Tumour Hepatocytes.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Liver-nervous system axis: pathways, dysregulation, and translational perspectives.Journal of neuroinflammation · 2026Review
- Role of central and peripheral serotonin in liver physiology and diseases.Theranostics · 2026Review
- Neural regulation of tumor progression: implications for hepatocellular carcinoma.Frontiers in immunology · 2026Review
- Liver-nervous system axis in MASLD: mechanistic insights and emerging targeted therapies.eGastroenterology · 2026Review
- The liver talks back: NPY orchestrates attraction of cancer cells and CHK2-dependent clonogenicity in the metastatic niche.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Autoimmunity in MASLD: Focus on autoantibodies, anti-apolipoprotein A1 IgG and G protein-coupled receptors.European journal of clinical investigation · 2025Review
- Roles of Peripheral Nerves in Tumor Initiation and Progression.International journal of molecular sciences · 2025Review
- Lipid Accumulation and Insulin Resistance: Bridging Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Kidney Disease.International journal of molecular sciences · 2025Review
- Bridging systemic metabolic dysfunction and Alzheimer's disease: the liver interface.Molecular neurodegeneration · 2025Review
- Multi-Organ Denervation: The Past, Present and Future.Journal of clinical medicine · 2025Review
- A Nerve-Fibroblast Axis in Mammalian Lung Fibrosis.bioRxiv : the preprint server for biology · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Sympathetic nerve signaling rewires the tumor microenvironment: a shift in "microenvironmental-ity".Cancer metastasis reviews · 2025Review
- Microbiota composition and intestinal barrier function modulated by tamsulosin andFrontiers in cellular and infection microbiology · 2025Article
- The role of hepatic sinusoidal microenvironment in NASH: pathogenesis, animal models, and therapeutic prospects.Frontiers in pharmacology · 2025Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundSympathetic nervous system (SNS) signalling regulates murine hepatic fibrogenesis through effects on hepatic stellate cells (HSC), and obesity-related hypertension with SNS activation accelerates progression of non-alcoholic fatty liver disease (NAFLD), the commonest cause of chronic liver disease. NAFLD may lead to cirrhosis. The effects of the SNS neurotransmitters norepinephrine (NE), epinephrine (EPI) and neuropeptide Y (NPY) on human primary HSC (hHSC) function and in NAFLD pathogenesis are poorly understood.
aimsto determine the mechanistic effects of NE/EPI/NPY on phenotypic changes in cultured hHSC, and to study SNS signalling in human NAFLD livers.
methodsFreshly isolated hHSC were assessed for expression of cathecholamine/neuropeptide Y receptors and for the synthesis of NE/EPI. The effects of NE/EPI/NPY and adrenoceptor antagonists prazosin (PRZ)/propranolol (PRL) on hHSC fibrogenic functions and the involved kinases and interleukin pathways were examined. Human livers with proven NAFLD were then assessed for upregulation of SNS signalling components.
resultsActivated hHSC express functional α/β-adrenoceptors and NPY receptors, which are upregulated in the livers of patients with cirrhotic NAFLD. hHSC in culture synthesize and release NE/EPI, required for their optimal basal growth and survival. Exogenous NE/EPI and NPY dose-dependently induced hHSC proliferation, mediated via p38 MAP, PI3K and MEK signalling. NE and EPI but not NPY increased expression of collagen-1α2 via TGF-β without involvement of the pro-fibrogenic cytokines leptin, IL-4 and IL-13 or the anti-fibrotic cytokine IL-10.
conclusionshHSC synthesize and require cathecholamines for optimal survival and fibrogenic functionality. Activated hHSC express directly fibrogenic α/β-adrenoceptors and NPY receptors, upregulated in human cirrhotic NAFLD. Adrenoceptor and NPY antagonists may be novel anti-fibrotic agents in human NAFLD.
Indexed as
Identifiers
What OpenQuestion holds
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.