Pathophysiologic role of hepatocyte nuclear factor 6

Hepatocyte nuclear factor 6 (HNF6) is one of liver-enriched transcription factors. HNF6 utilizes the bipartite onecut-homeodomain sequence to localize the HNF6 protein to the nuclear compartment and binds to specific DNA sequences of numerous target gene promoters. HNF6 regulates an intricate network and mediates complex biological processes that are best known in the liver and pancreas. The function of HNF6 is correlated to cell proliferation, cell cycle regulation, cell differentiation and organogenesis, cell migration and cell-matrix adhesion, glucose metabolism, bile homeostasis, inflammation and so on. HNF6 controls the transcription of its target genes in different ways. The details of the regulatory pathways and their mechanisms are still under investigation. Future study will explore HNF6 novel functions associated with apoptosis, oncogenesis, and modulation of the inflammatory response. This review highlights recent progression pertaining to the pathophysiologic role of HNF6 and summarizes the potential mechanisms in preclinical animal models. HNF6-mediated pathways represent attractive therapeutic targets for the treatment of the relative diseases such as cholestasis. (C) 2011 Elsevier Inc. All rights reserved.