Research ArticleFibrosis

Hexokinase 2 couples glycolysis with the profibrotic actions of TGF-β

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Science Signaling  17 Dec 2019:
Vol. 12, Issue 612, eaax4067
DOI: 10.1126/scisignal.aax4067

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Glycolysis promotes lung fibrosis

Transforming growth factor–β (TGF-β) promotes fibrosis by stimulating fibroblasts to proliferate and differentiate into matrix-secreting myofibroblasts. Yin et al. found that the glycolytic enzyme hexokinase 2 (HK2) was highly abundant in lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and that TGF-β induced the accumulation of HK2 and stimulated glycolysis in mouse and human lung fibroblasts. Pharmacological inhibition of HK2 with Lonidamine attenuated the profibrotic actions of TGF-β in fibroblasts. Lonidamine also reduced molecular markers of fibrosis and improved lung function in a mouse model of lung fibrosis. Thus, HK2-dependent metabolic dysregulation contributes to lung fibrosis and is a potential therapeutic target.

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