Krüppel-like factors and the liver

The Krüppel-like zinc finger transcription factor family encodes a family of proteins that currently includes at least 15 members regulating remarkably diverse processes, including cell growth, signal transduction, and differentiation. KLF genes are highly conserved evolutionarily with homologues expressed in zebrafish and Xenopus. The role of the Krüppel-like factor (KLF) family in the liver is equally diverse, with roles in the regulation of adipogenesis, gluconeogen-esis, apoptosis, cell cycle progression, cellular differentiation, energy homeostasis, oxidative stress, and hepatic stellate cell activation. Of the KLFs studied to date in the liver, KLF6 is the best characterized. This chapter therefore highlights the functional diversity of KLF6 in the liver with the understanding that it serves as a template for the study of other KLFs in the liver. Specifically, we focus on the KLF6 gene and its cloning and identification from activated hepatic stellate cells, the importance of alternative splicing in the regulation of KLF6 gene function, the contribution of the KLF family to liver development and injury, and finally, dysregulation of KLF6 function in disease through several important mechanisms including alternative splicing, decreased expression, loss of heterozygosity, and somatic mutation.