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

A. M. Diehl, M. Yin, J. Fleckenstein, S. Q. Yang, H. Z. Lin, D. A. Brenner, J. Westwick, G. Bagby, S. Nelson

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

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- α (TNF-α), 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-α 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.

Original languageEnglish
Pages (from-to)G552-G561
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume267
Issue number4 30-4
DOIs
StatePublished - 1994

Keywords

  • cytokines
  • proliferation

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