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Metabolic dysregulation into fibrosis

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Fibrosis Excessive fibrosis around alveoli, tiny air sacs that promote gas exchange, prevents the lungs from expanding properly. Yin et al. found that the glycolytic enzyme hexokinase 2 (HK2) was… Click to show full abstract

Fibrosis Excessive fibrosis around alveoli, tiny air sacs that promote gas exchange, prevents the lungs from expanding properly. Yin et al. found that the glycolytic enzyme hexokinase 2 (HK2) was abundant in lung fibroblasts from patients with idiopathic pulmonary fibrosis. The profibrotic cytokine transforming growth factor–β (TGF-β) induced HK2 accumulation in mouse and human lung fibroblasts and thus increased glycolysis in these cells. Inhibition of HK2 with the cancer drug lonidamine attenuated the profibrotic actions of TGF-β in fibroblasts and improved lung function in a mouse model of lung fibrosis. These results support a model of HK2-dependent metabolic dysregulation that contributes to lung fibrosis and demonstrates that HK2 is a potential therapeutic target. Sci. Signal. 12 , eaax4067 (2019).

Keywords: dysregulation fibrosis; fibrosis; metabolic dysregulation; hk2; lung

Journal Title: Science
Year Published: 2019

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