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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Longo, CR; Patel, VI; Shrikhande, GV; Scali, ST; Csizmadia, E; Daniel, S; Sun, DW; Grey, ST; Arvelo, MB; Ferran, C

Published Date

  • July 2005

Published In

Volume / Issue

  • 42 / 1

Start / End Page

  • 156 - 164

PubMed ID

  • 15962316

Pubmed Central ID

  • 15962316

Electronic International Standard Serial Number (EISSN)

  • 1527-3350

International Standard Serial Number (ISSN)

  • 0270-9139

Digital Object Identifier (DOI)

  • 10.1002/hep.20741

Language

  • eng