ArticleScientific reports2020
TGF-β1 is a regulator of the pyruvate dehydrogenase complex in fibroblasts.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
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- The mechano-immunological barrier in fibrosis-associated lung cancer: targeting matrix stiffness and the Piezo1 axis for microenvironment normalization.Frontiers in pharmacology · 2026Review
- Reprogramming of Mitochondrial and Cellular Energy Metabolism in Fibroblasts and Cardiomyocytes: Mechanisms and Therapeutic Strategies in Cardiac Fibrosis.Journal of cardiovascular translational research · 2025Review
- FGF2 supports NANOG expression via pyruvate dehydrogenase-dependent histone acetylation under low oxygen conditions.Frontiers in cell and developmental biology · 2025Article
- Ameliorative effect and potential mechanism of hyperoside on diabetic retinopathy.Frontiers in endocrinology · 2025Article
- Metabolic reprogramming and renal fibrosis: what role might Chinese medicine play?Chinese medicine · 2024Review
- NREP, transcriptionally upregulated by HIF-1α, aggravates breast cancer cell growth and metastasis by promoting glycolysis.Cell death discovery · 2024Article
- A two-way street - cellular metabolism and myofibroblast contraction.NPJ Regenerative medicine · 2024Review
- Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function.Biological research · 2024Article
- Fibrotic pathways and fibroblast-like synoviocyte phenotypes in osteoarthritis.Frontiers in immunology · 2024Review
- The immunometabolic ecosystem in cancer.Nature immunology · 2023Review
- A comprehensive cuproptosis score and associated gene signatures reveal prognostic and immunological features of idiopathic pulmonary fibrosis.Frontiers in immunology · 2023Article
- Propagation, Culture, and Characterization of Renal Fibroblasts.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The Interplay Between TGF-β Signaling and Cell Metabolism.Frontiers in cell and developmental biology · 2022Review
- Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases.Biomolecules · 2021Review
- A Metabolic Reprogramming of Glycolysis and Glutamine Metabolism Is a Requisite for Renal Fibrogenesis-Why and How?Frontiers in physiology · 2021Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TGF-β1 reprograms metabolism in renal fibroblasts, inducing a switch from oxidative phosphorylation to aerobic glycolysis. However, molecular events underpinning this are unknown. Here we identify that TGF-β1 downregulates acetyl-CoA biosynthesis via regulation of the pyruvate dehydrogenase complex (PDC). Flow cytometry showed that TGF-β1 reduced the PDC subunit PDH-E1α in fibroblasts derived from injured, but not normal kidneys. An increase in expression of PDH kinase 1 (PDK1), and reduction in the phosphatase PDP1, were commensurate with net phosphorylation and inactivation of PDC. Over-expression of mutant PDH-E1α, resistant to phosphorylation, ameliorated effects of TGF-β1, while inhibition of PDC activity with CPI-613 was sufficient to induce αSMA and pro-collagen I expression, markers of myofibroblast differentiation and fibroblast activation. The effect of TGF-β1 on PDC activity, acetyl-CoA, αSMA and pro-collagen I was also ameliorated by sodium dichloroacetate, a small molecule inhibitor of PDK. A reduction in acetyl-CoA, and therefore acetylation substrate, also resulted in a generalised loss of protein acetylation with TGF-β1. In conclusion, TGF-β1 in part regulates fibroblast activation via effects on PDC activity.
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