ArticleThe Journal of biological chemistry2018
Glutaminolysis is required for transforming growth factor-β1-induced myofibroblast differentiation and activation.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 2 of them syntheses that pooled it.
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Who cites it
115 citing papers in PubMed, 2 syntheses or guidelines pooled it, 157 citations in OpenAlex.
- Molecular Systems Architecture of Fibrotic Lung Microenvironment in Idiopathic Pulmonary Fibrosis.Cells · 2026Pooled it
- Genetic liability of gut microbiota for idiopathic pulmonary fibrosis and lung function: a two-sample Mendelian randomization study.Frontiers in cellular and infection microbiology · 2024Pooled it
- Mechanosignaling promotes macrophage apoptosis resistance in pulmonary fibrosisbioRxiv : the preprint server for biology · 2026Article
- Glutaminolysis and mTOR-C/EBPβ Signaling Drives the Differentiation of Novel IL-10-Producing Regulatory T Cells.International journal of molecular sciences · 2026Article
- Glutamine Metabolism: a Metabolic Hub Linking Vascular Remodeling and Plaque Stability in Atherosclerosis.Current atherosclerosis reports · 2026Review
- Organelle Crosstalk and Metabolic Reprogramming in Idiopathic Pulmonary Fibrosis: Mechanisms and Therapeutic Implications.Cell biochemistry and function · 2026Review
- Advances in metabolic reprogramming of pulmonary fibrosis.Chinese medical journal pulmonary and critical care medicine · 2026Review
- TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis.JCI insight · 2026Article
- Integrated Analysis of the Lung Microbiome and Metabolome Reveals Associations Between Amino Acid Metabolism and Pulmonary Fibrosis in a Bleomycin-Induced Mouse Model.International journal of molecular sciences · 2026Article
- Bidirectional Feedback Between Metabolic Reprogramming and Epithelial-Mesenchymal Transition: From Mechanisms to Therapeutic Interventions.Molecules (Basel, Switzerland) · 2026Review
- Doxorubicin exposure leads to cardiac fibroblast dysregulation and worsens fibrotic remodeling in the pathological heart.Journal of molecular and cellular cardiology plus · 2026Article
- Oncometabolite signatures from tumor-stroma crosstalk as potential non-invasive biomarkers.Cell death discovery · 2026Article
- Defective branched-chain amino acid catabolism promotes pulmonary fibrosis by inducing apoptosis resistance of myofibroblasts in mice.Cell communication and signaling : CCS · 2026Article
- GPT2-mediated Glutamate to α-Ketoglutaric Acid Conversion in Cardiac Fibroblast Promotes Fibrosis.JACC. Basic to translational science · 2026Article
- The Glutamine-α-Ketoglutarate Metabolic Axis Controls Vascular Smooth Muscle Cell Function.Cells · 2026Article
- Mitochondrial proteomics reveals reductive metabolism dependent on glutamine in fibroblasts of idiopathic pulmonary fibrosis under hypoxia.Scientific reports · 2026Article
- Targeting Cardiac Fibroblast Plasticity for Antifibrotic and Regenerative Therapy in Heart Failure.Cells · 2026Review
- Spatially resolved integrative analysis of transcriptomic and metabolomic changes in tissue injury studies.Nature communications · 2026Article
- Reprogrammed Fibrotic Niche Fuels Lung Cancer Initiation and Reciprocal Remodeling.International journal of biological sciences · 2026Review
- The role of glutamine metabolism in the pathogenesis of idiopathic pulmonary fibrosis and its therapeutic potential.Frontiers in oncology · 2026Review
55 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Myofibroblasts participate in physiological wound healing and pathological fibrosis. Myofibroblast differentiation is characterized by the expression of α-smooth muscle actin and extracellular matrix proteins and is dependent on metabolic reprogramming. In this study, we explored the role of glutaminolysis and metabolites of TCA in supporting myofibroblast differentiation. Glutaminolysis converts Gln into α-ketoglutarate (α-KG), a critical intermediate in the TCA cycle. Increases in the steady-state concentrations of TCA cycle metabolites including α-KG, succinate, fumarate, malate, and citrate were observed in TGF-β1-differentiated myofibroblasts. The concentration of glutamate was also increased in TGF-β1-differentiated myofibroblasts compared with controls, whereas glutamine levels were decreased, suggesting enhanced glutaminolysis. This was associated with TGF-β1-induced expression of the glutaminase (GLS) isoform, GLS1, which converts Gln into glutamate, at both the mRNA and protein levels. The stimulation of GLS1 expression by TGF-β1 was dependent on both SMAD3 and p38 mitogen-activated protein kinase activation. Depletion of extracellular Gln prevented TGF-β1-induced myofibroblast differentiation. The removal of extracellular Gln postmyofibroblast differentiation decreased the expression of the profibrotic markers fibronectin and hypoxia-inducible factor-1α and reversed TGF-β1-induced metabolic reprogramming. Silencing of GLS1 expression, in the presence of Gln, abrogated TGF-β1-induced expression of profibrotic markers. Treatment of GLS1-deficient myofibroblasts with exogenous glutamate or α-KG restored TGF-β1-induced expression of profibrotic markers in GLS1-deficient myofibroblasts. Together, these data demonstrate that glutaminolysis is a critical component of myofibroblast metabolic reprogramming that regulates myofibroblast differentiation.
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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.