Contradictory Role of Gadd45β in Liver Diseases

There are three homologous proteins (α, β and γ) in the growth arrest and DNA damage 45 (Gadd45) family. These proteins act as cellular responders to physiological and environmental stimuli. Gadd45β plays a significant role in the pathogenesis of liver diseases. Liver injury and growth stimulation increase expression of Gadd45β, which promotes cell survival, growth and proliferation in normal liver cells. By contrast, Gadd45β plays a role in promoting apoptosis and inhibiting tumour function in hepatocellular carcinoma (HCC). Currently, it is believed that Gadd45β benefits the liver through two different pathways: binding to MAPK kinase 6 (MKK6) to increase PCD induced by p38 (inhibiting tumours) or binding to constitutive androstane receptor (CAR) to jointly activate transcription of liver synthesis metabolism (promoting liver regeneration). This article aims to systematically review the role of Gadd45β in liver diseases, including its regulatory mechanism on expression and involvement in liver cell damage, inflammation, fibrosis and HCC. In conclusion, we explore the potential of targeting Gadd45β as a therapeutic strategy for liver diseases.