Source: International Congress 2014 – Cell biology 2014
Disease area: Airway diseases

Abstract

Background: COPD is characterised by small airway remodelling involving airway smooth muscle (ASM) thickening, in part, due to ASM cell (ASMC) hyperplasia. Transforming growth factor (TGF)-b, which is over-expressed in COPD lungs, is a potent inducer of ASMC hyperplasia. Metabolic deregulation involving increased glycolysis and decreased mitochondrial respiration (Warburg effect) has been linked to increased cell survival in pulmonary arterial hypertension and cancer. We hypothesised that TGF-b-induced ASMC hyperplasia is mediated by a shift in energy production to glycolysis. Aims and Objectives: Determine the effect of TGF-b on glycolytic and mitochondrial gene expression and the role of glycolysis in TGF-b-mediated ASMC proliferation. Methods: ASMCs were cultured from bronchoscopic biopsies of patients with COPD. mRNA expression was determined by real-time PCR. Cell proliferation was measured as rate of BrdU incorporation. Results: TGF-b (1ng/mL), in the presence of 2.5% foetal bovine serum (FBS), increased the mRNA levels of glucose transporter (GLUT)-1 (~3-fold), the rate-limiting glycolytic enzyme hexokinase (HK)-2 (~2-fold), the pyruvate dehydrogenase inhibitor, pyruvate dehydrogenase kinase (PDK)-1 (~3-fold) and lactate dehydrogenase (LDHA; ~4-fold). It also potently inhibited the mRNA expression of peroxisome proliferator-activated receptor-g coactivator (PGC)-1a (~90%), a key inducer of mitochondrial respiration. Inhibition of glycolysis using 2-deoxy-D-glucose (1-10mM) inhibited TGF-b and FBS-induced ASMC proliferation (~60%). Conclusion: TGF-b-induced ASMC proliferation may be mediated by a shift from mitochondrial respiration to glycolysis.

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Citations should be made in the following way:
C. Michaeloudes, I. Adcock, K. F. Chung (London, United Kingdom). The role of glycolysis in TGF-beta-mediated airway smooth muscle cell proliferation. Eur Respir J 2014; 44: Suppl. 58, 3843

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