ArticlePloS one2015
TGF-β1-mediated differentiation of fibroblasts is associated with increased mitochondrial content and cellular respiration.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 104 citations in OpenAlex.
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- Imaging methods to monitor and quantify cell differentiation.Frontiers in cell and developmental biology · 2025Review
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- Antioxidant, Antiinflammation, and Antifibrotic Activity of Ciplukan (Journal of inflammation research · 2024Article
- Significance of quantitative analyses of the impact of heterogeneity in mitochondrial content and shape on cell differentiation.Open biology · 2024Review
- Molecular and metabolomic characterization of hiPSC-derived cardiac fibroblasts transitioning to myofibroblasts.Frontiers in cell and developmental biology · 2024Article
- Metabolic mechanisms in physiological and pathological cardiac hypertrophy: new paradigms and challenges.Nature reviews. Cardiology · 2023Review
- Mitochondrial folate pathway regulates myofibroblast differentiation and silica-induced pulmonary fibrosis.Journal of translational medicine · 2023Article
- Cardiac fibroblasts and mechanosensation in heart development, health and disease.Nature reviews. Cardiology · 2023Review
- NADPH oxidase 4 is dispensable for skin myofibroblast differentiation and wound healing.Redox biology · 2023Article
- Protein conformation stabilized by newly formed turns for thermal resilience.Biophysical journal · 2023Article
- Article
- Generation and characterization of two immortalized dermal fibroblast cell lines from the spiny mouse (Acomys).PloS one · 2023Article
- Fucoxanthin Attenuates the Reprogramming of Energy Metabolism during the Activation of Hepatic Stellate Cells.Nutrients · 2022Article
- Pleiotropic Effects of Simvastatin and Losartan in Preclinical Models of Post-Traumatic Elbow Contracture.Frontiers in bioengineering and biotechnology · 2022Article
- Combined - whole blood and skin fibroblasts- transcriptomic analysis in Psoriatic Arthritis reveals molecular signatures of activity, resistance and early response to treatment.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
objectivsCytokine-dependent activation of fibroblasts to myofibroblasts, a key event in fibrosis, is accompanied by phenotypic changes with increased secretory and contractile properties dependent on increased energy utilization, yet changes in the energetic profile of these cells are not fully described. We hypothesize that the TGF-β1-mediated transformation of myofibroblasts is associated with an increase in mitochondrial content and function when compared to naive fibroblasts.
methodsCultured NIH/3T3 mouse fibroblasts treated with TGF-β1, a profibrotic cytokine, or vehicle were assessed for transformation to myofibroblasts (appearance of α-smooth muscle actin [α-SMA] stress fibers) and associated changes in mitochondrial content and functions using laser confocal microscopy, Seahorse respirometry, multi-well plate reader and biochemical protocols. Expression of mitochondrial-specific proteins was determined using western blotting, and the mitochondrial DNA quantified using Mitochondrial DNA isolation kit.
resultsTreatment with TGF-β1 (5 ng/mL) induced transformation of naive fibroblasts into myofibroblasts with a threefold increase in the expression of α-SMA (6.85 ± 0.27 RU) compared to cells not treated with TGF-β1 (2.52 ± 0.11 RU). TGF-β1 exposure increased the number of mitochondria in the cells, as monitored by membrane potential sensitive dye tetramethylrhodamine, and expression of mitochondria-specific proteins; voltage-dependent anion channels (0.54 ± 0.05 vs. 0.23 ± 0.05 RU) and adenine nucleotide transporter (0.61 ± 0.11 vs. 0.22 ± 0.05 RU), as well as mitochondrial DNA content (530 ± 12 μg DNA/106 cells vs. 307 ± 9 μg DNA/106 cells in control). TGF-β1 treatment was associated with an increase in mitochondrial function with a twofold increase in baseline oxygen consumption rate (2.25 ± 0.03 vs. 1.13 ± 0.1 nmol O2/min/106 cells) and FCCP-induced mitochondrial respiration (2.87 ± 0.03 vs. 1.46 ± 0.15 nmol O2/min/106 cells).
conclusionsTGF-β1 induced differentiation of fibroblasts is accompanied by energetic remodeling of myofibroblasts with an increase in mitochondrial respiration and mitochondrial content.
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