ArticlePloS one2017
Regulation of hepatic stellate cell proliferation and activation by glutamine metabolism.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
- Chronic attenuation of brain leptin signalling is associated with early metabolic dysfunction in lean rats.The Journal of physiology · 2026Article
- The Hidden Metabolites in Glutinous Rice Huangjiu and Their Antioxidant Potential.Foods (Basel, Switzerland) · 2026Article
- From metabolic antagonism to homeostatic restoration: rewiring hepatic stellate cell bioenergetics for liver fibrosis reversal.Frontiers in medicine · 2026Review
- Metabolic reprogramming in hepatic stellate cells: unveiling a novel therapeutic target for liver fibrosis.Frontiers in physiology · 2026Review
- Immunonutrition: Another Player on the MASLD Field.International journal of molecular sciences · 2025Review
- Metabolic Sparks in the Liver: Metabolic and Epigenetic Reprogramming in Hepatic Stellate Cells Activation and Its Implications for Human Metabolic Diseases.Diabetes & metabolism journal · 2025Review
- Integrative Multiomics Analysis Identifies HK2 as a Key Regulator of Metabolic Reprogramming in Hepatic Stellate Cells.Human mutation · 2025Article
- Exploring the Antifibrotic Mechanisms of Ghrelin: Modulating TGF-β Signalling in Organ Fibrosis.Expert reviews in molecular medicine · 2024Review
- Review
- Atractylenolide III Ameliorates Bile Duct Ligation-Induced Liver Fibrosis by Inhibiting the PI3K/AKT Pathway and Regulating Glutamine Metabolism.Molecules (Basel, Switzerland) · 2023Article
- Organoids: Construction and Application in Gastric Cancer.Biomolecules · 2023Review
- Remodeling the hepatic fibrotic microenvironment with emerging nanotherapeutics: a comprehensive review.Journal of nanobiotechnology · 2023Review
- The Hepatic Mitochondrial Pyruvate Carrier as a Regulator of Systemic Metabolism and a Therapeutic Target for Treating Metabolic Disease.Biomolecules · 2023Review
- The role of hepatic microenvironment in hepatic fibrosis development.Annals of medicine · 2022Review
- Liver organoids: an in vitro 3D model for liver cancer study.Cell & bioscience · 2022Review
- Fibrogenic Pathways in Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD).International journal of molecular sciences · 2022Review
- Glutaminolysis-ammonia-urea Cycle Axis, Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies.Journal of clinical and translational hepatology · 2022Review
- Metabolic Regulation of Fibroblast Activation and Proliferation during Organ Fibrosis.Kidney diseases (Basel, Switzerland) · 2022Review
- Integrated Microbiome and Metabolome Analysis Reveals Correlations Between Gut Microbiota Components and Metabolic Profiles in Mice with Methotrexate-Induced Hepatoxicity.Drug design, development and therapy · 2022Article
- Transcriptome and proteome profiling of activated cardiac fibroblasts supports target prioritization in cardiac fibrosis.Frontiers in cardiovascular medicine · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Liver fibrosis is the excessive accumulation of extracellular matrix proteins, which is mainly caused by accumulation of activated hepatic stellate cells (HSCs). The mechanisms of activation and proliferation of HSCs, two key events after liver damage, have been studied for many years. Here we report a novel pathway to control HSCs by regulating glutamine metabolism. We demonstrated that the proliferation of HSCs is critically dependent on glutamine that is used to generate α-ketoglutarate (α-KG) and non-essential amino acid (NEAA). In addition, both culture- and in vivo-activated HSCs have increased glutamine utilization and increased expression of genes related to glutamine metabolism, including GLS (glutaminase), aspartate transaminase (GOT1) and glutamate dehydrogenase (GLUD1). Inhibition of these enzymes, as well as glutamine depletion, had a significant inhibitory effect on HSCs activation. In addition to providing energy expenditure, conversion of glutamine to proline is enhanced. The pool of free proline may also be increased via downregulation of POX expression. Hedgehog signaling plays an important role in the regulation of glutamine metabolism, as well as TGF-β1, c-Myc, and Ras signalings, via transcriptional upregulation and repression of key metabolic enzymes in this pathway. Finally, changes in glutamine metabolism were also found in mouse liver tissue following CCl4-induced acute injury.
conclusionGlutamine metabolism plays an important role in regulating the proliferation and activation of HSCs. Strategies that are targeted at glutamine metabolism may represent a novel therapeutic approach to the treatment of liver fibrosis.
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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.