Role of Glycogen Synthase Kinase-3 in Interferon-γ-Mediated Immune Hepatitis

Glycogen synthase kinase-3 (GSK-3), a serine/threonine kinase, is a vital glycogen synthase regulator controlling glycogen synthesis, glucose metabolism, and insulin signaling. GSK-3 is widely expressed in different types of cells, and its abundant roles in cellular bioregulation have been speculated. Abnormal GSK-3 activation and inactivation may affect its original bioactivity. Moreover, active and inactive GSK-3 can regulate several cytosolic factors and modulate their diverse cellular functional roles. Studies in experimental liver disease models have illustrated the possible pathological role of GSK-3 in facilitating acute hepatic injury. Pharmacologically targeting GSK-3 is therefore suggested as a therapeutic strategy for liver protection. Furthermore, while the signaling transduction of GSK-3 facilitates proinflammatory interferon (IFN)-gamma in vitro and in vivo, the blockade of GSK-3 can be protective, as shown by an IFN-gamma-induced immune hepatitis model. In this study, we explored the possible regulation of GSK-3 and the potential relevance of GSK-3 blockade in IFN-gamma-mediated immune hepatitis.

Automated summary

GSK-3 is a vital regulator of glycogen synthesis that plays a crucial role in cellular bioregulation. Abnormal GSK-3 activation and inactivation can lead to liver damage. Targeting GSK-3 with drugs is a potential therapeutic approach for liver protection. Additionally, blocking GSK-3 has a protective effect in IFN-gamma-mediated immune hepatitis.