ArticleJournal of cellular and molecular medicine2020
Metabolic reprogramming of glycolysis and glutamine metabolism are key events in myofibroblast transition in systemic sclerosis pathogenesis.
Article in Journal of cellular and molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 75 citations in OpenAlex.
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Mitochondrial Dysregulation and Molecular Signaling in Systemic Sclerosis Cardiac Disease: An Integrative Echocardiographic, Microvascular, and Biomarker Review.International journal of molecular sciences · 2026Review
- Linezolid-mediated Prevention of Fibroblast Activation and Tissue Fibrosis via Mitochondrial Translation Inhibition.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Atrial fibroblast metabolic reprogramming in atrial fibrillation: a candidate mechanism within multicellular atrial cardiomyopathy.Frontiers in cardiovascular medicine · 2026Review
- The TREM2 paradox in fibrosis: a unified mechanism for opposite outcomes across organs.Frontiers in immunology · 2026Review
- Pyruvate kinase M2 is elevated in systemic sclerosis and plays a role in its pathogenesis.Frontiers in immunology · 2026Article
- Integrating Single-Cell Transcriptomics and Mendelian Randomization to Identify RAC1 as a Causal Metabolic Driver of Pericyte Dysfunction in Systemic Sclerosis.Mediators of inflammation · 2026Article
- The effects of combined low-dose cadmium and deltamethrin on mitochondrial bioenergetics and metabolism in human lung fibroblasts.Toxicology reports · 2025Article
- [Research progress on cellular metabolic reprogramming in skin fibrosis].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Review
- Article
- Pyruvate kinase splice variants in fibroblasts influence cardiac remodeling after myocardial infarction in male mice.Journal of molecular and cellular cardiology · 2025Article
- NMR based clinical metabolomics revealed altered lipid and sugar metabolism in systemic sclerosis with implications for diagnosis and therapeutic strategies.Scientific reports · 2025Article
- Serum Metabolomic Profiling Reveals Differences Between Systemic Sclerosis Patients with Polyneuropathy.International journal of molecular sciences · 2025Article
- METTL3 promotes the hypertrophic scar fibrosis via m6A RNA methylation of GRAMD1B mRNA.Journal of molecular histology · 2025Article
- Nutrition and Diet Patterns as Key Modulators of Metabolic Reprogramming in Melanoma Immunotherapy.Journal of clinical medicine · 2025Review
- Inhibition of adenosine/A2A receptor signaling suppresses dermal fibrosis by enhancing fatty acid oxidation.Cell communication and signaling : CCS · 2025Article
- The Pathophysiological Role of Mitochondrial Oxidative Stress in Rheumatic Diseases.Journal of inflammation research · 2025Review
- PDK2-enhanced glycolysis aggravates fibrosis via IL11 signaling pathway in Graves' orbitopathy.Frontiers in immunology · 2025Article
- Identification of the Metabolic Characteristic of Organ Fibrosis Using Microbial Analysis on RNA-seq Data.Current gene therapy · 2025Article
- Exposure of Primary Human Skin Fibroblasts to Carbon Dioxide-Containing Solution Significantly Reduces TGF-β-Induced Myofibroblast Differentiation In Vitro.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Systemic Sclerosis (SSc) is a rare fibrotic autoimmune disorder for which no curative treatments currently exist. Metabolic remodelling has recently been implicated in other autoimmune diseases; however, its potential role in SSc has received little attention. Here, we aimed to determine whether changes to glycolysis and glutaminolysis are important features of skin fibrosis. TGF-β1, the quintessential pro-fibrotic stimulus, was used to activate fibrotic pathways in NHDFs in vitro. Dermal fibroblasts derived from lesions of SSc patients were also used for in vitro experiments. Parameters of glycolytic function were assessed using by measuring extracellular acidification in response to glycolytic activators/inhibitors, whilst markers of fibrosis were measured by Western blotting following the use of the glycolysis inhibitors 2-dg and 3PO and the glutaminolysis inhibitor G968. Succinate was also measured after TGF-β1 stimulation. Itaconate was added to SSc fibroblasts and collagen examined. TGF-β1 up-regulates glycolysis in dermal fibroblasts, and inhibition of glycolysis attenuates its pro-fibrotic effects. Furthermore, inhibition of glutamine metabolism also reverses TGF-β1-induced fibrosis, whilst glutaminase expression is up-regulated in dermal fibroblasts derived from SSc patient skin lesions, suggesting that enhanced glutamine metabolism is another aspect of the pro-fibrotic metabolic phenotype in skin fibrosis. TGF-β1 was also able to enhance succinate production, with increased succinate shown to be associated with increased collagen expression. Incubation of SSc cells with itaconate, an important metabolite, reduced collagen expression. TGF-β1 activation of glycolysis is a key feature of the fibrotic phenotype induced by TGF-B1 in skin cells, whilst increased glutaminolysis is also evident in SSc fibroblasts.
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