Liver-enriched transcription factor expression relates to chronic hepatic failure in humans

Hepatology Communications
Jorge Guzman-LepeAlejandro Soto-Gutierrez

Abstract

The mechanisms by which the liver fails in end-stage liver disease remain elusive. Disruption of the transcription factor network in hepatocytes has been suggested to mediate terminal liver failure in animals. However, this hypothesis remains unexplored in human subjects. To study the relevance of transcription factor expression in terminal stages of chronic liver failure in humans, we analyzed the expression of liver-enriched transcription factors (LETFs) hepatocyte nuclear factor (HNF)4α, HNF1α, forkhead box protein A2 (FOXA2), CCAAT/enhancer-binding protein (CEBP)α, and CEBPβ. We then selected downstream genes responsible for some hepatic functions (ornithine transcarbamylase [OTC], cytochrome P450 3A4 [CYP3A4], coagulation factor VII [F7], cadherin 1 [CDH1], phospho-ezrin (Thr567)/radixin (Thr564)/moesin (Thr558) [p-ERM], phospho-myosin light chain [p-MLC], low-density lipoprotein receptor-related protein 1 [LRP1]) in liver tissue from patients at different stages of decompensated liver function based upon Child-Pugh classification, Model for End-Stage Liver Disease score, and degree of inflammatory activity/fibrosis. We first examined differential expression of LETF and determined whether a relationship exists between tran...Continue Reading

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Citations

Jun 4, 2020·Hepatology Communications·Rodrigo M FlorentinoAlejandro Soto-Gutierrez
Feb 6, 2021·Cellular and Molecular Gastroenterology and Hepatology·Marc-Olivier DeguiseRashmi Kothary
May 16, 2021·Seminars in Liver Disease·Nils HaepAlejandro Soto-Gutierrez
Aug 6, 2021·Journal of Hepatocellular Carcinoma·Yihong SunKeyue Ding

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