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A20 protects mice from lethal radical hepatectomy by promoting hepatocyte proliferation via a p21waf1-dependent mechanism.

Publication ,  Journal Article
Longo, CR; Patel, VI; Shrikhande, GV; Scali, ST; Csizmadia, E; Daniel, S; Sun, DW; Grey, ST; Arvelo, MB; Ferran, C
Published in: Hepatology
July 2005

The liver has a remarkable regenerative capacity, allowing recovery following injury. Regeneration after injury is contingent on maintenance of healthy residual liver mass, otherwise fulminant hepatic failure (FHF) may arise. Understanding the protective mechanisms safeguarding hepatocytes and promoting their proliferation is critical for devising therapeutic strategies for FHF. We demonstrate that A20 is part of the physiological response of hepatocytes to injury. In particular, A20 is significantly upregulated in the liver following partial hepatectomy. A20 protects hepatocytes from apoptosis and ongoing inflammation by inhibiting NF-kappaB. Hepatic expression of A20 in BALB/c mice dramatically improves survival following extended and radical lethal hepatectomy. A20 expression in the liver limits hepatocellular damage hence maintains bilirubin clearance and the liver synthetic function. In addition, A20 confers a proliferative advantage to hepatocytes via decreased expression of the cyclin-dependent kinase inhibitor p21(waf1). In conclusion, A20 provides a proliferative advantage to hepatocytes. By combining anti-inflammatory, antiapoptotic and pro-proliferative functions, A20-based therapies could be beneficial in prevention and treatment of FHF.

Duke Scholars

Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

July 2005

Volume

42

Issue

1

Start / End Page

156 / 164

Location

United States

Related Subject Headings

  • Zinc Fingers
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Survival Analysis
  • Regeneration
  • Recovery of Function
  • Proteins
  • Nuclear Proteins
  • Models, Animal
  • Mice
  • Liver Regeneration
 

Citation

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Longo, C. R., Patel, V. I., Shrikhande, G. V., Scali, S. T., Csizmadia, E., Daniel, S., … Ferran, C. (2005). A20 protects mice from lethal radical hepatectomy by promoting hepatocyte proliferation via a p21waf1-dependent mechanism. Hepatology, 42(1), 156–164. https://doi.org/10.1002/hep.20741
Longo, Christopher R., Virendra I. Patel, Gautam V. Shrikhande, Salvatore T. Scali, Eva Csizmadia, Soizic Daniel, David W. Sun, Shane T. Grey, Maria B. Arvelo, and Christiane Ferran. “A20 protects mice from lethal radical hepatectomy by promoting hepatocyte proliferation via a p21waf1-dependent mechanism.Hepatology 42, no. 1 (July 2005): 156–64. https://doi.org/10.1002/hep.20741.
Longo CR, Patel VI, Shrikhande GV, Scali ST, Csizmadia E, Daniel S, et al. A20 protects mice from lethal radical hepatectomy by promoting hepatocyte proliferation via a p21waf1-dependent mechanism. Hepatology. 2005 Jul;42(1):156–64.
Longo, Christopher R., et al. “A20 protects mice from lethal radical hepatectomy by promoting hepatocyte proliferation via a p21waf1-dependent mechanism.Hepatology, vol. 42, no. 1, July 2005, pp. 156–64. Pubmed, doi:10.1002/hep.20741.
Longo CR, Patel VI, Shrikhande GV, Scali ST, Csizmadia E, Daniel S, Sun DW, Grey ST, Arvelo MB, Ferran C. A20 protects mice from lethal radical hepatectomy by promoting hepatocyte proliferation via a p21waf1-dependent mechanism. Hepatology. 2005 Jul;42(1):156–164.
Journal cover image

Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

July 2005

Volume

42

Issue

1

Start / End Page

156 / 164

Location

United States

Related Subject Headings

  • Zinc Fingers
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Survival Analysis
  • Regeneration
  • Recovery of Function
  • Proteins
  • Nuclear Proteins
  • Models, Animal
  • Mice
  • Liver Regeneration