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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2019; 25(30): 4074-4091
Published online Aug 14, 2019. doi: 10.3748/wjg.v25.i30.4074
Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases
Matthew M Yeh, Dustin E Bosch, Sayed S Daoud
Matthew M Yeh, Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, United States
Dustin E Bosch, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, United States
Sayed S Daoud, Department of Pharmaceutical Sciences, Washington State University Health Sciences, Spokane, WA 99210, United States
Author contributions: All authors reviewed the literature and wrote the manuscript; YMM and Daoud SS edited the paper and final approval of the final version.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Sayed S Daoud, PhD, Associate Professor, Director, Department of Pharmaceutical Sciences, Washington State University Health Sciences, 412 Spokane Falls Blvd, Spokane, WA 99210, United States. daoud@wsu.edu
Telephone: +1-509-3686572 Fax: +1-509-3686561
Received: March 26, 2019
Peer-review started: March 26, 2019
First decision: April 30, 2019
Revised: July 15, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: August 14, 2019
Processing time: 141 Days and 20.3 Hours
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: Hepatocyte nuclear factor 4-alpha; Liver cirrhosis; Hepatocellular carcinoma; Viral hepatitis; Gastrointestinal tract; Colorectal carcinoma; Transcription factor

Core tip: Our current understanding of the molecular etiology of human liver and gastrointestinal diseases is limited and there is a critical need to explore novel hypotheses and risk factors that may contribute to these diseases. Hepatocyte nuclear factor 4-alpha (HNF4α) has been well recognized as an important transcription factor that regulates gene expression involved in the differentiation of liver and gastrointestinal cells. Dysregulation of HNF4α function is associated with many diseases related to these cells. Here we attempt to update our understanding on the role of HNF4α in the pathogenesis of these diseases for use as target for better therapeutic modality.