Hepatic β-arrestins: potential roles in liver health and disease

Abstract

Β-arrestins are intracellular scaffolding proteins that have multifaceted roles in different types of disorders. In this review article, we gave a summary about the discovery, characterization and classification of these proteins and their intracellular functions. Moreover, this review article focused on the hepatic expression of β-arrestins and their hepatocellular distribution and function in each liver cell type. Also, we showed that β-arrestins are key regulators of distinct types of hepatic disorders. On the other hand, we addressed some important points that have never been studied before regarding the role of β-arrestins in certain types of hepatic disorders which needs more research efforts to cover.

Keywords: Hepatic disorders; Hepatocellular carcinoma; Liver fibrosis; β-arrestin-1; β-arrestin-2.

Fig. 1

A graphical summary of β-arrestins signaling in the different types of hepatic cells. LPS lipopolysaccharides, TLR4 toll like receptor 4, NF-κB nuclear factor κB, TNF-α tumor necrosis factor α, IL-1β,-6,-10 interleukin-1β,-6, 10, RIG-I retinoic acid-inducible gene I, VISA virus-induced signaling adaptor, MITA mediator of interferon regulatory transcription factor 3 activation, TBK1 TANK binding kinase 1, IRF3 interferon regulatory factor 3, GCGR Gs-coupled glucagon receptor, cAMP Cyclic adenosine monophosphate, PKA protein kinase A, GIT1 G-protein coupled receptor kinase-interacting protein 1, eNOS endothelial nitric oxide synthase, HSC hepatic stellate cells, ERK extracellular regulating kinase JNK c-Jun N-terminal kinase, NOX4 NADPH oxidase 4, ROS reactive oxygen species, TRIII type 3 transforming growth factor β1, Akt protein kinase B, ECM extracellular matrix. Upward arrows refer to increased expression or activity of the listed proteins. Downward arrows refer to decreased expression or activity of the listed proteins

Fig. 2

A Graphical summary of the roles of β-arrestins in hepatic disorders. PBC primary biliary cholangitis, INF interferon, HCC hepatocellular carcinoma, MAPK mitogen activated protein kinase, ERK extracellular regulating kinase, PI3K phosphatidyl inositol 3 kinase, Akt protein kinase B, NF-κB: nuclear factor Κb, TNF-α tumor necrosis factor α, ALD alcoholic liver disease, α-SMA α smooth muscle actin, NASH non-alcoholic steatohepatitis, GDF15 growth differentiation factor 15. Upward arrows refer to increased expression or activity of the listed proteins. Downward arrows refer to decreased expression or activity of the listed proteins