Mechanisms and Opportunities of the Arrestin Beta Signaling Pathway in Liver Diseases.

Arrestin beta 1 (ARRB1) and ARRB2, which are multifunctional adapters in G protein-coupled receptor signaling, are highly involved in liver-related diseases. ARRB1 plays a protective role against ischemia-reperfusion injury, acute liver injury, and nonalcoholic fatty liver disease by inhibiting apoptosis and improving metabolic disorders. ARRB1 has been reported to be protective in mouse liver fibrosis models; however, it has also been shown to have pathogenic effects in human liver fibrosis. This discrepancy may be due to limitations in mouse models and species differences. In contrast, ARRB2 has dual functions in liver-related diseases. On the contrary, it reduces acute hepatitis and ischemic injury by inhibiting the NF-κB/c-Jun N-terminal kinase pathway. On the contrary, it accelerates disease progression by activating macrophages and promoting oxidative stress and collagen deposition in autoimmune hepatitis, alcoholic steatohepatitis, and fibrosis. Furthermore, the structural differences between ARRB1 and ARRB2 may determine their signal bias through nuclear output capability, nuclear input capability, and phosphorylation. In-depth analysis of the interaction between ARRBs and their signaling mechanisms is expected to provide accurate therapeutic targets for liver disease.