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).
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