RT Journal Article SR Electronic T1 β-Arrestin Deficiency Protects Against Pulmonary Fibrosis in Mice and Prevents Fibroblast Invasion of Extracellular Matrix JF Science Translational Medicine FD American Association for the Advancement of Science SP 74ra23 OP 74ra23 DO 10.1126/scitranslmed.3001564 VO 3 IS 74 A1 Lovgren, Alysia Kern A1 Kovacs, Jeffrey J. A1 Xie, Ting A1 Potts, Erin N. A1 Li, Yuejuan A1 Foster, W. Michael A1 Liang, Jiurong A1 Meltzer, Eric B. A1 Jiang, Dianhua A1 Lefkowitz, Robert J. A1 Noble, Paul W. YR 2011 UL http://stm.sciencemag.org/content/3/74/74ra23.abstract AB Idiopathic pulmonary fibrosis is a progressive disease that causes unremitting extracellular matrix deposition with resulting distortion of pulmonary architecture and impaired gas exchange. β-Arrestins regulate G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors through receptor desensitization while also acting as signaling scaffolds to facilitate numerous effector pathways. Here, we examine the role of β-arrestin1 and β-arrestin2 in the pathobiology of pulmonary fibrosis. In the bleomycin-induced mouse lung fibrosis model, loss of either β-arrestin1 or β-arrestin2 resulted in protection from mortality, inhibition of matrix deposition, and protected lung function. Fibrosis was prevented despite preserved recruitment of inflammatory cells and fibroblast chemotaxis. However, isolated lung fibroblasts from bleomycin-treated β-arrestin–null mice failed to invade extracellular matrix and displayed altered expression of genes involved in matrix production and degradation. Furthermore, knockdown of β-arrestin2 in fibroblasts from patients with idiopathic pulmonary fibrosis attenuated the invasive phenotype. These data implicate β-arrestins as mediators of fibroblast invasion and the development of pulmonary fibrosis, and as a potential target for therapeutic intervention in patients with idiopathic pulmonary fibrosis.