Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases

Hepatocyte nuclear factor 4-alpha (HNF4 alpha) is a highly conserved member of nuclear receptor superfamily of ligand-dependent transcription factors that is expressed in liver and gastrointestinal organs (pancreas, stomach, and intestine). In liver, HNF4 alpha is best known for its role as a master regulator of liver-specific gene expression and essential for adult and fetal liver function. Dysregulation of HNF4 alpha expression has been associated with many human diseases such as ulcerative colitis, colon cancer, maturity-onset diabetes of the young, liver cirrhosis, and hepatocellular carcinoma. However, the precise role of HNF4 alpha in the etiology of these human pathogenesis is not well understood. Limited information is known about the role of HNF4 alpha isoforms in liver and gastrointestinal disease progression. There is, therefore, a critical need to know how disruption of the expression of these isoforms may impact on disease progression and phenotypes. In this review, we will update our current understanding on the role of HNF4 alpha in human liver and gastrointestinal diseases. We further provide additional information on possible use of HNF4 alpha as a target for potential therapeutic approaches.