Evidence map›Paper›PMID 32490322›Full record

ArticleHepatology communications2020

Cellular Location of HNF4α is Linked With Terminal Liver Failure in Humans.

Rodrigo M Florentino, Nicolas A Fraunhoffer, Kazutoyo Morita, Kazuki Takeishi, Alina Ostrowska, Abhinav Achreja, Olamide Animasahun, Nils Haep, Shohrat Arazov, Nandini Agarwal and 13 more

Open access · goldAbstract read
In one paragraph

Article in Hepatology communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.9field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 31 citations in OpenAlex.

  1. Gene-Based Clustering Identifies QSOX1 and IL1RAP as Biomarkers of Metabolic Dysfunction-Associated Steatotic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
  2. Article
  3. Article
  4. Hepatocyte Nuclear Factor 4 Alpha: A Key Regulator of Liver Disease Pathology and Haemostatic Disorders.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  5. Article
  6. Structural insights into the HNF4 biology.Frontiers in endocrinology · 2023
    Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 6 institutions in 5 countries.

Rodrigo M FlorentinoDepartment of Pathology University of Pittsburgh Pittsburgh PA.
Nicolas A FraunhofferDepartment of Pathology University of Pittsburgh Pittsburgh PA.
Kazutoyo MoritaDepartment of Pathology University of Pittsburgh Pittsburgh PA.
Kazuki TakeishiDepartment of Pathology University of Pittsburgh Pittsburgh PA.
Alina OstrowskaDepartment of Surgery Children's Hospital of Pittsburgh of UPMC University of Pittsburgh Pittsburgh PA.
Abhinav AchrejaLaboratory for Systems Biology of Human Diseases Department of Biomedical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI.
Olamide AnimasahunLaboratory for Systems Biology of Human Diseases Department of Biomedical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI.
Nils HaepDepartment of Pathology University of Pittsburgh Pittsburgh PA.
Shohrat ArazovDepartment of Pathology University of Pittsburgh Pittsburgh PA.
Nandini AgarwalDepartment of Pathology University of Pittsburgh Pittsburgh PA.
Alexandra Collin de l'HortetDepartment of Pathology University of Pittsburgh Pittsburgh PA.
Jorge Guzman-LepeDepartment of Pathology University of Pittsburgh Pittsburgh PA.
Edgar N TafalengDepartment of Surgery Children's Hospital of Pittsburgh of UPMC University of Pittsburgh Pittsburgh PA.
Amitava MukherjeeDepartment of Surgery Children's Hospital of Pittsburgh of UPMC University of Pittsburgh Pittsburgh PA.
Kris TroyDepartment of Biological Sciences University of Pittsburgh Pittsburgh PA.
Swati BanerjeeDepartment of Pathology University of Pittsburgh Pittsburgh PA.
Shirish ParanjpeDepartment of Pathology University of Pittsburgh Pittsburgh PA.
George K MichalopoulosDepartment of Pathology University of Pittsburgh Pittsburgh PA.
Aaron BellDepartment of Pathology University of Pittsburgh Pittsburgh PA.
Deepak NagrathLaboratory for Systems Biology of Human Diseases Department of Biomedical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI.
Sarah J HainerDepartment of Biological Sciences University of Pittsburgh Pittsburgh PA.
Ira J FoxDepartment of Surgery Children's Hospital of Pittsburgh of UPMC University of Pittsburgh Pittsburgh PA.
Alejandro Soto-GutierrezDepartment of Pathology University of Pittsburgh Pittsburgh PA.
University of Pittsburgh · USUniversity of Michigan–Ann Arbor · USChildren's Hospital of Pittsburgh · USFundación Centro de Estudios Infectológicos · ARKyushu University · JPUniversidade Federal de Minas Gerais · BR

Funding

Treating AT Deficiency with Drugs that Modulate the Proteostasis NetworkP01DK096990 · NIDDK · WASHINGTON UNIVERSITY · PI FOX, IRA J. · 2012 to 2023
$18.3M
Harnessing human brain and liver microphysiological systems for testing therapeutics for metastatic melanomaU01TR002383 · NCATS · VANDERBILT UNIVERSITY · PI MURPHY, WILLIAM L., TAYLOR, D. LANSING · 2018 to 2022
$7.6M
Human Microphysiology Systems Disease Model of Type 2 Diabetes Starting with Liver and pancreatic IsletsUH3DK119973 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, D. LANSING · 2020 to 2022
$6.7M
Chromatin-mediated mechanisms of transcription regulation in ES cellsR35GM133732 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Sarah Jane Hainer · 2019 to 2026
$3.5M
Mini-Livers Derived from Human IPS Cells for Modeling Steatosis and TherapyR01DK099257 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NAGRATH, DEEPAK, SOTO-GUTIERREZ, ALEJANDRO · 2014 to 2024
$3.4M
Applying a Human Liver Microphysiology System to Develop Therapeutic Strategies for Non-Alcoholic Fatty Liver Disease (NAFLD)R01DK117881 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, D. LANSING · 2018 to 2021
$2.7M
Targeting Stromal Influences on Glutamine Addiction in Ovarian CancerR01CA227622 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MOK, SAMUEL C, NAGRATH, DEEPAK · 2018 to 2022
$2.3M
Human Microphysiology Systems Disease Model of Type 2 Diabetes Starting with Liver and pancreatic IsletsUG3DK119973 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, D. LANSING · 2018 to 2019
$2.3M
Identification of USP13 as a therapeutic target for ovarian cancerR01CA222251 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI LU, XIONGBIN, NAGRATH, DEEPAK · 2018 to 2022
$1.8M
Uncovering Role of Exosomes in Regulating Pancreatic Cancer Cell MetabolismR01CA204969 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NAGRATH, DEEPAK · 2017 to 2021
$1.7M
NCATS NIH HHS U01 TR002383NCI NIH HHS R01 CA204969NCI NIH HHS R01 CA222251NCI NIH HHS R01 CA227622NIDDK NIH HHS P01 DK096990NIDDK NIH HHS R01 DK099257NIDDK NIH HHS R01 DK117881NIDDK NIH HHS UG3 DK119973NIDDK NIH HHS UH3 DK119973NIGMS NIH HHS R35 GM133732
6 · The paper itself

Abstract

Hepatocyte nuclear factor 4 alpha (HNF4α) is a transcription factor that plays a critical role in hepatocyte function, and HNF4α-based reprogramming corrects terminal liver failure in rats with chronic liver disease. In the livers of patients with advanced cirrhosis, HNF4α RNA expression levels decrease as hepatic function deteriorates, and protein expression is found in the cytoplasm. These findings could explain impaired hepatic function in patients with degenerative liver disease. In this study, we analyzed HNF4α localization and the pathways involved in post-translational modification of HNF4α in human hepatocytes from patients with decompensated liver function. RNA-sequencing analysis revealed that AKT-related pathways, specifically phospho-AKT, is down-regulated in cirrhotic hepatocytes from patients with terminal failure, in whom nuclear levels of HNF4α were significantly reduced, and cytoplasmic expression of HNF4α was increased. cMET was also significantly reduced in failing hepatocytes. Moreover, metabolic profiling showed a glycolytic phenotype in failing human hepatocytes. The contribution of cMET and phospho-AKT to nuclear localization of HNF4α was confirmed using Spearman's rank correlation test and pathway analysis, and further correlated with hepatic dysfunction by principal component analysis. HNF4α acetylation, a posttranslational modification important for nuclear retention, was also significantly reduced in failing human hepatocytes when compared with normal controls.

Identifiers

PMID32490322
PMCPMC7262291
OpenAlexW3019909510

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.