@article {1503139,
	title = {Screening for YAP Inhibitors Identifies Statins as Modulators of Fibrosis},
	journal = {Am J Respir Cell Mol Biol},
	volume = {62},
	number = {4},
	year = {2020},
	month = {2020 Apr},
	pages = {479-492},
	abstract = {Idiopathic pulmonary fibrosis is a lung disease with limited therapeutic options that is characterized by pathological fibroblast activation and aberrant lung remodeling with scar formation. YAP (Yes-associated protein) is a transcriptional coactivator that mediates mechanical and biochemical signals controlling fibroblast activation. In this study, we developed a high-throughput small-molecule screen for YAP inhibitors in primary human lung fibroblasts. Multiple HMG-CoA (hydroxymethylglutaryl-coenzyme A) reductase inhibitors (statins) were found to inhibit YAP nuclear localization via induction of YAP phosphorylation, cytoplasmic retention, and degradation. We further show that the mevalonate pathway regulates YAP activation, and that simvastatin treatment reduces fibrosis markers in activated human lung fibroblasts and in the bleomycin mouse model of pulmonary fibrosis. Finally, we show that simvastatin modulates YAP  in mouse lung fibroblasts. Our results highlight the potential of small-molecule screens for YAP inhibitors and provide a mechanism for the antifibrotic activity of statins in idiopathic pulmonary fibrosis.},
	issn = {1535-4989},
	doi = {10.1165/rcmb.2019-0296OC},
	author = {Santos, Daniela M and Pantano, Lorena and Pronzati, Gina and Grasberger, Paula and Probst, Clemens K and Black, Katharine E and Spinney, Jillian J and Hariri, Lida P and Nichols, Royale and Lin, Yufei and Bieler, Michael and Seither, Peter and Nicklin, Paul and Wyatt, David and Tager, Andrew M and Medoff, Benjamin D}
}
