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Metabolic re-patterning in chronic obstructive pulmonary disease airway smooth muscle cells
Michaeloudes, Charalambos Kuo, Chih-Hsi Haji, Gulam Finch, Donna Halayko, Andrew J Kirkham, Paul Chung, Kian Fan Adcock, Ian
Michaeloudes, Charalambos
Kuo, Chih-Hsi
Haji, Gulam
Finch, Donna
Halayko, Andrew J
Kirkham, Paul
Chung, Kian Fan
Adcock, Ian
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2017-11-30
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Abstract
COPD airways are characterised by airway smooth muscle (ASM) thickening, partly due to ASM 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 non-smokers, 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, up-regulation of the pentose phosphate pathway product ribose-5- phosphate and of nucleotide biosynthesis intermediates, and increased levels of the glutamine catabolite glutamate. TGF-β/FBS-stimulated COPD ASMCs also 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.
Citation
Michaeloudes C., Kuo CH., Haji G., Finch DK., Halayko AJ., Kirkham P., Chung KF., Adcock IM. Metabolic re-patterning in COPD airway smooth muscle cells, European Respiratory Journal, 50(5) doi: 10.1183/13993003.00202
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Journal article
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en
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© 2017 The Authors. Published by European Respiratory Journal. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: 10.1183/13993003.00202-2017
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0903-193
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MRC-ABPI COPDMAP consortium G1001367/1