ArticleCell death & disease2022
Targeting glutamine metabolism in hepatic stellate cells alleviates liver fibrosis.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Tea and liver fibrosis: a bibliometric analysis of mechanisms, translational challenges, and emerging trends.Frontiers in nutrition · 2026Pooled it
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Integrative metabolomics and malonyl-proteomics reveal the crosstalk between metabolic reprogramming and lysine malonylation in liver fibrosis.Journal of physiology and biochemistry · 2026Article
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- A novel glutamine metabolism-based classification system for characterizing the heterogeneity of hepatocellular carcinoma.Journal of gastrointestinal oncology · 2026Article
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- Urea cycle dysregulation and arginine pathways in the pathogenesis of NAFLD and NASH (Review).International journal of molecular medicine · 2026Review
- Review
- Emerging roles of SIRT6 and its modulators in kidney diseases.Cell death discovery · 2026Review
- Thioredoxin system dysregulation and calpain activation drive myocardial disulfidptosis via pathological disulfide bonds remodeling.Cell death discovery · 2026Article
- Metabolic reprogramming in fibrosis-related diseases: underlying mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Green tea polyphenol-iron oxide chitosan nanoparticles modulate gut microbiota and regulate metabolic pathways.World journal of microbiology & biotechnology · 2026Article
- Beyond deacetylation: crosstalk mechanisms and context-dependent regulation of sirtuin non-classical enzymatic functions in disease.Molecular medicine (Cambridge, Mass.) · 2026Review
- Metabolic Pathways Linking Atherosclerotic Cardiovascular Disease With Metabolic Dysfunction-Associated Steatotic Liver Disease.Current atherosclerosis reports · 2026Review
- Pirfenidone Sensitizes Hepatic Stellate Cells to Ferroptosis by Reprogramming Glutamine and Serine Metabolism for GSH Depletion.Antioxidants (Basel, Switzerland) · 2026Article
- Amino Acids-Potential Biomarkers of Histological Features for MASLD in Pediatric Obesity.International journal of molecular sciences · 2026Review
- Effect of free fatty acids on TGF-β1 mediated fibrogenesis in hepatic stellate cells.Molecular metabolism · 2026Article
- Hepato-renal Protective Effect of Glutamine in Oxidative Stress Rat Model by Elevating the Glutamine-Glutathione Axis.International journal of preventive medicine · 2026Article
- RIMKLA promotes hypertension by activating PKM2 to trigger VSMC phenotype switch.Military Medical Research · 2026Article
- Amino Acid Metabolism in Chronic Liver Disease: from Pathogenic Driver to Therapeutic Target.International journal of biological sciences · 2026Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glutamine metabolism plays an essential role in cell growth, and glutamate dehydrogenase (GDH) is a key enzyme. GDH promotes the metabolism of glutamate and glutamine to generate ATP, which is profoundly increased in multiple human cancers. Through in vitro and in vivo experiments, we verified that the small-molecule GDH inhibitor EGCG slowed the progression of fibrosis by inhibiting GDH enzyme activity and glutamine metabolism. SIRT4 is a mitochondrial enzyme with NAD that promotes ADP ribosylation and downregulates GDH activity. The role of SIRT4 in liver fibrosis and the related mechanisms are unknown. In this study, we measured the expression of SIRT4 and found that it was downregulated in liver fibrosis. Modest overexpression of SIRT4 protected the liver from fibrosis by inhibiting the transformation of glutamate to 2-ketoglutaric acid (α-KG) in the tricarboxylic acid cycle (TCA), thereby reducing the proliferative activity of hepatic stellate cells (HSCs). Collectively, our study reveals that SIRT4 controls GDH enzyme activity and expression, targeting glutamine metabolism in HSCs and alleviating 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.