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Review
. 2019 Aug 14;25(30):4074-4091.
doi: 10.3748/wjg.v25.i30.4074.

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

Matthew M Yeh  1 , Dustin E Bosch  2 , Sayed S Daoud  3
Affiliations
Review

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

Matthew M Yeh et al. World J Gastroenterol. .

Abstract

Hepatocyte nuclear factor 4-alpha (HNF4α) 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, HNF4α 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 HNF4α 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 HNF4α in the etiology of these human pathogenesis is not well understood. Limited information is known about the role of HNF4α 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 HNF4α in human liver and gastrointestinal diseases. We further provide additional information on possible use of HNF4α as a target for potential therapeutic approaches.

Keywords: Colorectal carcinoma; Gastrointestinal tract; Hepatocellular carcinoma; Hepatocyte nuclear factor 4-alpha; Liver cirrhosis; Transcription factor; Viral hepatitis.

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Conflict of interest statement

Conflict-of-interest statement: No potential conflicts of interest. No financial support.

Figures

Figure 1
Figure 1
Overview of regulatory and target genes involved in differentiated and de-differentiated stages of liver development. Examples of relevant HNF4α target genes identified by our group[27] are individually numbered.
Figure 2
Figure 2
Differentially expressed proteins in normal and liver disease states. Heat maps of differentially expressed proteins (DEPs) (truncated) that were selected following supervised analysis (A) Normal vs. Cirrhosis, (B) Normal vs. Hepatocellular carcinoma, (C) Cirrhosis vs. Hepatocellular carcinoma, and (D) Venn Diagram comparing the significantly DEPs identified. (E) Interactive Network Analysis of DEPs in cirrhosis and hepatocellular carcinoma as compared to normal shows HNF4α as a focus hub to many DEPs. (F) A representative of immunoblot analysis of TF and APOA1 (upper panel), HNF4α (lower panel) in tissue samples of AA & CA. GAPDH was used as a loading control, as published in[23].
Figure 3
Figure 3
Differential expression of hepatocyte nuclear factor 4alpha in cirrhotic and hepatocellular carcinoma livers. Representative H&E and P1/P2 HNF4α stained samples of HCV cirrhotic and hepatocellular carcinoma of Caucasian (A) and African American (B) tissue samples, as published in[27].
Figure 4
Figure 4
Immunoreactivity of hepatocyte nuclear factor 4alpha isoforms in cirrhotic and hepatocellular carcinoma livers. Data are presented as the mean ± standard error (n=4 tissue sections from 24 paraffin embedded tissue blocks). Data were evaluated for stastistical significance by one-way analysis of variance and are represented as follows: aP<0.05, bP<0.001as compared to normal for P1/P2 HNF4α (A) and P1- HNF4α (B). Black bar (CA) = Caucasian Americans; Gray bar (AA) = African Americans, as published in[27]
See this image and copyright information in PMC

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