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Metabolic re-patterning in COPD airway smooth muscle cells.

Metabolic re-patterning in COPD airway smooth muscle cells.
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Michaeloudes C, Kuo CH, Haji G, Finch DK, Halayko AJ, Kirkham P, Chung KF, Adcock IM, ,


Michaeloudes C, Kuo CH, Haji G, Finch DK, Halayko AJ, Kirkham P, Chung KF, Adcock IM, , (click to view)

Michaeloudes C, Kuo CH, Haji G, Finch DK, Halayko AJ, Kirkham P, Chung KF, Adcock IM, ,

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The European respiratory journal 2017 11 3050(5) pii 1700202
Abstract

Chronic obstructive pulmonary disease (COPD) airways are characterised by thickening of airway smooth muscle, partly due to airway smooth muscle cell (ASMC) hyperplasia. Metabolic reprogramming involving increased glycolysis and glutamine catabolism supports the biosynthetic and redox balance required for cellular growth. We examined whether COPD ASMCs show a distinct metabolic phenotype that may contribute to increased growth.We performed an exploratory intracellular metabolic profile analysis of ASMCs from healthy nonsmokers, healthy smokers and COPD patients, under unstimulated or growth conditions of transforming growth factor (TGF)-β and fetal bovine serum (FBS).COPD ASMCs showed impaired energy balance and accumulation of the glycolytic product lactate, glutamine, fatty acids and amino acids compared to controls in unstimulated and growth conditions. Fatty acid oxidation capacity was reduced under unstimulated conditions. TGF-β/FBS-stimulated COPD ASMCs showed restoration of fatty acid oxidation capacity, upregulation of the pentose phosphate pathway product ribose-5-phosphate and of nucleotide biosynthesis intermediates, and increased levels of the glutamine catabolite glutamate. In addition, TGF-β/FBS-stimulated COPD ASMCs showed a higher reduced-to-oxidised glutathione ratio and lower mitochondrial oxidant levels. Inhibition of glycolysis and glutamine depletion attenuated TGF-β/FBS-stimulated growth of COPD ASMCs.Changes in glycolysis, glutamine and fatty acid metabolism may lead to increased biosynthesis and redox balance, supporting COPD ASMC growth.

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