Tumor necrosis factor-alpha induces c-jun during the regenerative response to liver injury.

Published

Journal Article

After liver injury, remaining hepatocytes proliferate to regenerate the liver. Although the precise mechanisms that initiate and localize regeneration are unknown, local induction of c-jun is a critical, early step in the response. Treatment of rats with antibodies to tumor necrosis factor-alpha (TNF-alpha), a mediator of liver injury, inhibits regenerative induction of jun nuclear kinase activity and nuclear c-jun expression and alters the DNA binding activity of the c-jun transcription factor, AP-1, in liver. Pretreatment with anti-TNF antibodies does not affect pulmonary or renal c-jun expression or AP-1 binding activity post-partial hepatectomy. In primary hepatocyte cultures, TNF-alpha directly promotes the proliferative actions of mitogens, supporting in vivo evidence that it sensitizes hepatocytes to mitogens. Thus local release of TNF may act in a paracrine fashion to initiate regeneration in the injured liver by promoting induction of critical growth-related genes, such as c-jun.

Full Text

Duke Authors

Cited Authors

  • Diehl, AM; Yin, M; Fleckenstein, J; Yang, SQ; Lin, HZ; Brenner, DA; Westwick, J; Bagby, G; Nelson, S

Published Date

  • October 1994

Published In

Volume / Issue

  • 267 / 4 Pt 1

Start / End Page

  • G552 - G561

PubMed ID

  • 7943321

Pubmed Central ID

  • 7943321

Electronic International Standard Serial Number (EISSN)

  • 2163-5773

International Standard Serial Number (ISSN)

  • 0002-9513

Digital Object Identifier (DOI)

  • 10.1152/ajpgi.1994.267.4.g552

Language

  • eng