Beta-Catenin and the Survival of Hepatocytes

The Wnt/β-catenin pathway is critical for liver development, differentiation, metabolism, and homeostasis. Aberrations in this pathway have also been identified in many pathophysiological conditions, such as nonalcoholic steatohepatitis, fibrosis, and hepatobiliary neoplasias. Recent research has uncovered a role for Wnt/β-catenin signaling in regulating cell survival or cell death after acute or chronic liver injury as well. In this chapter, we will provide background on this signaling pathway as well as various mechanisms involved in apoptosis and survival in both experimental and clinical models of liver injury. We will then discuss the role of Wnt/β-catenin signaling in the context of various types of liver injury, focusing on two types of regulation: direct (through transcription of target genes and physical interaction with survival pathway components) and indirect (through regulation of processes such as oxidative stress and inflammation during liver injury). Finally, we will discuss the therapeutic implications of modulating this pathway to impact cell survival during liver injury.