Β‐Arrestin1 enhances liver fibrosis through autophagy‐mediated Snail signaling. Issue 2 (14th September 2018)

• Record Type: Journal Article
• Authors: Tan, Siwei; Lu, Yu; Xu, Minyi; Huang, Xiaoli; Liu, Huiling; Jiang, Jie; Wu, Bin
• Is Part Of: FASEB journal. Volume 33:Issue 2(2019)
• Page Start: 2000
• Page End: 2016
• Publication Date: 2018-09-14
• Subjects: hepatocytes -- proliferation -- hepatic stellate cells -- activation -- GSK-3β; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201800828RR
• Languages: English
• ISSNs: 0892-6638

Abstract

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 β‐arr1 promotes liver fibrosis via autophagy‐mediated Snail signaling, and β‐arr1 may be a therapeutic target for liver fibrosis.—Tan, S., Lu, Y., Xu, M., Huang, X., Liu, H., Jiang, J., Wu, B. β‐Arrestinl enhances liver fibrosis through autophagy‐mediated Snail signaling. FASEB J. 33, 2000–2016 (2019). www.fasebj.org