Resetting the transcription factor network reverses terminal chronic hepatic failure

The Journal of Clinical Investigation
Taichiro NishikawaIra J Fox

Abstract

The cause of organ failure is enigmatic for many degenerative diseases, including end-stage liver disease. Here, using a CCl4-induced rat model of irreversible and fatal hepatic failure, which also exhibits terminal changes in the extracellular matrix, we demonstrated that chronic injury stably reprograms the critical balance of transcription factors and that diseased and dedifferentiated cells can be returned to normal function by re-expression of critical transcription factors, a process similar to the type of reprogramming that induces somatic cells to become pluripotent or to change their cell lineage. Forced re-expression of the transcription factor HNF4α induced expression of the other hepatocyte-expressed transcription factors; restored functionality in terminally diseased hepatocytes isolated from CCl4-treated rats; and rapidly reversed fatal liver failure in CCl4-treated animals by restoring diseased hepatocytes rather than replacing them with new hepatocytes or stem cells. Together, the results of our study indicate that disruption of the transcription factor network and cellular dedifferentiation likely mediate terminal liver failure and suggest reinstatement of this network has therapeutic potential for correcting o...Continue Reading

References

Jan 1, 1976·Methods in Cell Biology·P O Seglen
Nov 1, 1991·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A Martinez-Hernandez, J Martinez
May 1, 1989·Scandinavian Journal of Gastroenterology·M VaubourdolleR Poupon
Mar 25, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·N KobayashiI J Fox
May 10, 2002·Nucleic Acids Research·Richard M Cawthon
Feb 20, 2003·Journal of Hepatology·Scott L Friedman
Jun 28, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Carmen BerasainJesús Prieto
Apr 16, 2004·The New England Journal of Medicine·Pere GinèsJuan Rodés
Mar 22, 2005·Journal of Hepatology·François Durand, Dominique Valla
Apr 11, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jinah Choi, J-H James Ou
Jun 2, 2006·Molecular Systems Biology·Duncan T OdomRichard A Young
Feb 29, 2008·Drug Metabolism and Pharmacokinetics·Frank J Gonzalez
Mar 11, 2008·Lancet·Detlef Schuppan, Nezam H Afdhal
Jun 25, 2008·Laboratory Investigation; a Journal of Technical Methods and Pathology·Pallavi B LimayeErin R Ochoa
Mar 18, 2009·Bioinformatics·Cole TrapnellSteven L Salzberg
Dec 19, 2009·The American Journal of Pathology·George K Michalopoulos
Jan 8, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Eugene BolotinFrances M Sladek
Aug 27, 2010·Journal of Hepatology·Matthew HoareGraeme Alexander
Jan 29, 2011·Current Drug Targets·Ignazio GrattaglianoPiero Portincasa
May 21, 2011·Bioinformatics·Julien Lajugie, Eric E Bouhassira
Nov 24, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Liping LiuIra J Fox
Apr 6, 2013·Nature Medicine·Young-Jae NamEric N Olson

❮ Previous
Next ❯

Citations

Jun 20, 2015·Cellular and Molecular Life Sciences : CMLS·Carmen Berasain, Matías A Avila
Dec 25, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·A Collin de l'HortetA Soto-Gutierrez
Jan 13, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Seema S DesaiTammy T Chang
Mar 13, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Marzena Swiderska-SynAnna Mae Diehl
Aug 25, 2016·Cellular Signalling·Rebecca VasconcellosRodrigo R Resende
Oct 27, 2016·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Jason A Wertheim
Mar 10, 2017·Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society·Zahida KhanSarangarajan Ranganathan
Nov 16, 2017·Scientific Reports·Wei WangWei-Fen Xie
Dec 7, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ian HuckUdayan Apte
May 8, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Bharat BhushanGeorge K Michalopoulos
Sep 1, 2017·Science Translational Medicine·Zhongwei CaoBi-Sen Ding
Aug 19, 2020·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Paulo FontesEric Lagasse
Nov 19, 2015·Médecine sciences : M/S·Hélène Gilgenkrantz, Pascale Bossard
May 16, 2018·Hepatology Communications·Jorge Guzman-LepeAlejandro Soto-Gutierrez
Feb 6, 2020·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Inês Cebola
Aug 23, 2019·World Journal of Gastroenterology : WJG·Matthew M YehSayed S Daoud
Jun 4, 2020·Hepatology Communications·Rodrigo M FlorentinoAlejandro Soto-Gutierrez
Feb 6, 2021·Cellular and Molecular Gastroenterology and Hepatology·Marc-Olivier DeguiseRashmi Kothary
Feb 3, 2021·Gastroenterology·Don C Rockey, Scott L Friedman
Dec 28, 2016·Matrix Biology : Journal of the International Society for Matrix Biology·Tammy T ChangValerie M Weaver
Apr 16, 2021·Expert Opinion on Emerging Drugs·Jonathan Andrew FallowfieldAndrew Robertson
Jun 28, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Alexandre J DebackerNagy Habib
May 16, 2021·Seminars in Liver Disease·Nils HaepAlejandro Soto-Gutierrez
Aug 29, 2021·Journal of Hepatology·Taihua YangAmar Deep Sharma
Feb 13, 2018·Gastroenterology·Chen ChenBart Spee
Jun 26, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·María Gárate-RascónCarmen Berasain

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
RNA-Seq
FCS
transfection
dot blot
ELISA

Software Mentioned

ImageJ
SPSS
TopHat
GenPlay

Related Concepts

Related Feeds

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.