Fatty acid synthase is required for profibrotic TGF-β signaling

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Mi-Yeon JungEdward B Leof

Abstract

Evidence is provided that the fibroproliferative actions of TGF-β are dependent on a metabolic adaptation that sustains pathologic growth. Specifically, profibrotic TGF-β signaling is shown to require fatty acid synthase (FASN), an essential anabolic enzyme responsible for the de novo synthesis of fatty acids. With the use of pharmacologic and genetic approaches, we show that TGF-β-stimulated FASN expression is independent of Smad2/3 and is mediated via mammalian target of rapamycin complex 1. In the absence of FASN activity or protein, TGF-β-driven fibrogenic processes are reduced with no apparent toxicity. Furthermore, as increased FASN expression was also observed to correlate with the degree of lung fibrosis in bleomycin-treated mice, inhibition of FASN was examined in a murine-treatment model of pulmonary fibrosis. Remarkably, inhibition of FASN not only decreased expression of profibrotic targets, but lung function was also stabilized/improved, as assessed by peripheral blood oxygenation.-Jung, M.-Y., Kang, J.-H., Hernandez, D. M., Yin, X., Andrianifahanana, M., Wang, Y., Gonzalez-Guerrico, A., Limper, A. H., Lupu, R., Leof, E. B. Fatty acid synthase is required for profibrotic TGF-β signaling.

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Citations

Sep 25, 2019·Nature Reviews. Drug Discovery·Xiao ZhaoFei-Fei Liu
Feb 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Danielle M HernandezEdward B Leof
Jul 2, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chao SunXinhui Liu
Jul 31, 2019·Nature Communications·Kuei-Pin ChungAugustine M K Choi
Jan 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jeong-Han KangEdward B Leof
Dec 19, 2019·Science Signaling·Xueqian YinEdward B Leof
Jan 5, 2021·The FEBS Journal·Robert B Hamanaka, Gökhan M Mutlu
Mar 15, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yan-Nan YouYuan-Yuan Ding
Apr 11, 2021·Kidney International·Vanderlene L KungEdmund Huang
Aug 26, 2021·Science Signaling·Brintha SelvarajahRachel C Chambers
Aug 31, 2021·The International Journal of Biochemistry & Cell Biology·Chuin Ying UngTanya J Shaw
Oct 27, 2021·Cancer Biology & Therapy·Vinod S BishtKiran Ambatipudi
Dec 23, 2021·JCI Insight·Shailza SharmaCarol Feghali-Bostwick

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