Metabolic Reprogramming Is Required for Myofibroblast Contractility and Differentiation
| Autor: | Sunad Rangarajan, Naomi J. Logsdon, Benjamin P. Persons, Jaroslaw W. Zmijewski, Victor M. Darley-Usmar, Karen Bernard, Saranya Ravi, Gang Liu, Victor J. Thannickal, Kasturi Mitra, Na Xie |
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| Rok vydání: | 2015 |
| Předmět: |
MAPK/ERK pathway
Mitochondrion Biology p38 Mitogen-Activated Protein Kinases Biochemistry Cell Line Electron Transport Transforming Growth Factor beta1 Oxygen Consumption medicine Humans Glycolysis Myofibroblasts Lung Molecular Biology Skeletal muscle Cell Differentiation Cell Biology TFAM Mitochondria Cell biology Metabolism medicine.anatomical_structure Mitochondrial biogenesis Anaerobic glycolysis Energy Metabolism Myofibroblast |
| Zdroj: | Journal of Biological Chemistry. 290:25427-25438 |
| ISSN: | 0021-9258 |
| Popis: | Contraction is crucial in maintaining the differentiated phenotype of myofibroblasts. Contraction is an energy-dependent mechanism that relies on the production of ATP by mitochondria and/or glycolysis. Although the role of mitochondrial biogenesis in the adaptive responses of skeletal muscle to exercise is well appreciated, mechanisms governing energetic adaptation of myofibroblasts are not well understood. Our study demonstrates induction of mitochondrial biogenesis and aerobic glycolysis in response to the differentiation-inducing factor transforming growth factor β1 (TGF-β1). This metabolic reprogramming is linked to the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Inhibition of p38 MAPK decreased accumulation of active peroxisome proliferator-activated receptor γ coactivator 1α in the nucleus and altered the translocation of mitochondrial transcription factor A to the mitochondria. Genetic or pharmacologic approaches that block mitochondrial biogenesis or glycolysis resulted in decreased contraction and reduced expression of TGF-β1-induced α-smooth muscle actin and collagen α-2(I) but not of fibronectin or collagen α-1(I). These data indicate a critical role for TGF-β1-induced metabolic reprogramming in regulating myofibroblast-specific contractile signaling and support the concept of integrating bioenergetics with cellular differentiation. |
| Databáze: | OpenAIRE |
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