β-Arrestin1 enhances liver fibrosis through autophagy-mediated Snail signaling

Abstract

GPCR mediator β-arrestins (β-arr1 and β-arr2) regulate a variety of physiologic and pathologic processes, including hepatocellular carcinogenesis. However, the role of β-arrestins in liver fibrosis remains unknown. β-arr1, but not β-arr2, was upregulated in liver fibrotic tissues in both humans and mice; moreover, autophagy was increased. β-arr1 deficiency or autophagic inhibitor 3-methyladenine (3-MA) significantly blocked autophagy and downregulated liver fibrosis. Furthermore, β-arr1 enhanced hepatocyte compensatory proliferation, and hepatic stellate cell growth with activation via autophagy resulted in liver fibrosis. In the fibrosis, β-arr1 promoted nuclear translocation of Snail by downregulation of glycogen synthase kinase-3β, and the nuclear translocation of Snail was abrogated either by β-arr1 deficiency or by 3-MA. These results suggest that b-arr1 promotes liver fibrosis via autophagy-mediated Snail signaling, and b-arr1 may be a therapeutic target for liver fibrosis.-Tan, S., Lu, Y., Xu, M., Huang, X., Liu, H., Jiang, J., Wu, B. b-Arrestin1 enhances liver fibrosis through autophagy-mediated Snail signaling.