Fatty acid synthase is required for profibrotic TGF‐β signaling

• DOI: 10.1096/fj.201701187r
• Publication Date: 2018-02-16T19:41:44Z
• Authors: Mi‐Yeon Jung; Jeong‐Han Kang; Danielle M. Herna...; Xueqian Yin; Mahefatiana Andri...; Youli Wang; Anatilde Gonzalez...; Andrew H. Limper; Edward B. Leof
• Keywords: 0301 basic medicine; 0303 health sciences; Pulmonary Fibrosis; Smad Proteins; Cell Line; Fatty Acid Synthase, Type I; Mice, Inbred C57BL; Bleomycin; Mice; 03 medical and health sciences; Transforming Growth Factor beta; Animals; 10. No inequality; Signal Transduction

Evidence is provided that the fibroproliferative actions of TGF-β are dependent on a metabolic adaptation sustains pathologic growth. Specifically, profibrotic signaling shown to require fatty acid synthase (FASN), an essential anabolic enzyme responsible for de novo synthesis acids. With use pharmacologic and genetic approaches, we show TGF-β-stimulated FASN expression independent Smad2/ 3 mediated via mammalian target rapamycin complex 1. In absence activity or protein, -driven fibrogenic processes reduced with no apparent toxicity. Furthermore, as increased was also observed correlate degree lung fibrosis in bleomycin-treated mice, inhibition examined murine-treatment model pulmonary fibrosis. Remarkably, not only decreased targets, but function stabilized/improved, assessed by peripheral blood oxygenation.—Jung, M.-Y., Kang, J.-H., Hernandez, D. M., Yin, X., Andrianifahanana, Wang, Y., Gonzalez-Guerrico, A., Limper, A. H., Lupu, R., Leof, E. B. Fatty required signaling. FASEB J. 32, 3803–3815 (2018). www.fasebj.org