Polymer-Functionalized Mitochondrial Transplantation to Fibroblasts Counteracts a Pro-Fibrotic Phenotype
Abstract
:1. Introduction
2. Results and Discussion
2.1. TGF-β Stimulation of Fibroblasts Promoted Myofibroblast Differentiation and a Pro-Fibrogenic Programming
2.2. TGF-β Stimulation of Fibroblasts Led to Metabolic Reprogramming of Fibroblasts towards Glycolysis
2.3. Dex-TPP/Mt Underwent Uptake by TGF-β-Stimulated Fibroblasts
2.4. Dex-TPP/Mt Altered the Metabolic Phenotype of TGF-β-Stimulated Fibroblasts
2.5. Dex-TPP/Mt Counteracted the Pro-Fibrotic Phenotype and Cell Dynamics of TGF-β-Stimulated Fibroblasts
3. Materials and Methods
3.1. Materials
3.2. Animals
3.3. Dex-TPP Synthesis, Characterization, and Functionalization of Isolated Mitochondria
3.4. Fluorescence Microscopy Examination of Fibronectin and α-Smooth Muscle Actin Expression
3.5. Flow Cytometry and Confocal Microscopy for Uptake Examination
3.6. Western Blot
3.7. MTT Assay
3.8. Extracellular Flux Analysis
3.9. ATP and Glucose Consumption Assays
3.10. ROS Examination
3.11. Cell Proliferation Evaluation
3.12. Cell Migration Studies
3.13. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ATCC | American Type Culture Collection |
BMDM | Bone marrow-derived macrophage |
cAMP | 3′, 5′ cyclic adenosine monophosphate |
CMs | Cardiomyocytes |
Col1 | Type 1 collagen |
DAPI | 4′,6-diamidino-2-phenylindole |
Dex | Dextran |
Dex-TPP/Mt | Dextran and triphenylphosphonium mitochondria |
DMSO | Dimethyl sulfoxide |
ECAR | Extracellular acidification rate |
ECM | Extracellular matrix |
EMEM | Eagle’s Minimum Essential Medium |
ETC | Electron transport chain |
FAK | Focal adhesive kinase |
FGF-2 | Fibroblast growth factor 2 |
FITC | Fluorescein isothiocyanate |
FMT | Fibroblast-to-myofibroblast transition |
FN | Fibronectin |
FRNK | FAK-related nonkinase |
HF | High-fat |
HIF-1α | Hypoxia-inducible factor-1α |
HK2 | Hexokinase-2 |
hVFF | Human vocal fold fibroblasts |
I/R | Ischemia-reperfusion |
IPF | Idiopathic pulmonary fibrosis |
LDH | Lactate dehydrogenase |
mtROS | Mitochondrial reactive oxygen species |
MTT | 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide |
NAFLD | Nonalcoholic fatty liver disease |
NASH | Nonalcoholic steatohepatitis |
NOX4 | NADPH oxidase 4 |
NT | Non-treated |
OCR | Oxygen consumption rate |
OXPHOS | Oxidative phosphorylation |
PDGF-BB | Platelet-derived growth factor-BB |
PEP | Phosphoenolpyruvate |
PFA | Paraformaldehyde |
PGDM | Pregestational diabetes mellitus |
PHD2 | Prolyl hydroxylase domain-containing protein 2 |
PHDH1-A | Acti-Stain 555 Phalloidin |
PKM2 | Pyruvate kinase isozyme M2 |
ROS | Reactive oxygen species |
SCI | Spinal cord injury |
SEM | Standard error of the mean |
TGF-β | Transforming growth factor-β |
TNBC | Triple negative breast cancer |
TPP | Triphenylphosphonium |
TPP-COOH | Triphenylphosphonium bromide |
VEGF | Vascular endothelial growth factor |
αSMA | α-smooth muscle actin |
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Baudo, G.; Wu, S.; Massaro, M.; Liu, H.; Lee, H.; Zhang, A.; Hamilton, D.J.; Blanco, E. Polymer-Functionalized Mitochondrial Transplantation to Fibroblasts Counteracts a Pro-Fibrotic Phenotype. Int. J. Mol. Sci. 2023, 24, 10913. https://doi.org/10.3390/ijms241310913
Baudo G, Wu S, Massaro M, Liu H, Lee H, Zhang A, Hamilton DJ, Blanco E. Polymer-Functionalized Mitochondrial Transplantation to Fibroblasts Counteracts a Pro-Fibrotic Phenotype. International Journal of Molecular Sciences. 2023; 24(13):10913. https://doi.org/10.3390/ijms241310913
Chicago/Turabian StyleBaudo, Gherardo, Suhong Wu, Matteo Massaro, Haoran Liu, Hyunho Lee, Aijun Zhang, Dale J. Hamilton, and Elvin Blanco. 2023. "Polymer-Functionalized Mitochondrial Transplantation to Fibroblasts Counteracts a Pro-Fibrotic Phenotype" International Journal of Molecular Sciences 24, no. 13: 10913. https://doi.org/10.3390/ijms241310913