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

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136 Scopus citations


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
Issue number4 30-4
StatePublished - 1994


  • cytokines
  • proliferation


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