Growth differentiation factor-15: Induction in liver injury through p53 and tumor necrosis factor-independent mechanisms

Teresa A. Zimmers, Xiaoling Jin, Edward C. Hsiao, Eduardo A. Perez, Robert H. Pierce, Kenneth D. Chavin, Leonidas G. Koniaris

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Expression of macrophage inhibitory cytokine-1 (MIC-1), a divergent transforming growth factor-β family member, and its murine ortholog, growth/differentiation factor-15 (GDF-15), is induced in hepatocytes by surgical and chemical injury and heat shock. Here, we demonstrate that the regulation of GDF-15/MIC-1 expression may be evolutionarily conserved because MIC-1 was induced in diseased human livers. Gdf15 induction was independent of protein synthesis, a hallmark of immediate-early gene regulation. Although tumor necrosis factor (TNF) induced GDF-15 expression, injury-elicited Gdf15 expression was not reduced in mice deficient for both TNF receptor subtypes. Furthermore, although the stress sensor p53 is known to induce GDF-15/MIC-1 expression, injury-elicited Gdf15 expression was unchanged in p53 null mice. Our results demonstrate that GDF-15 induction is an immediate early response to liver injury that can occur through TNF and p53 independent pathways.

Original languageEnglish (US)
Pages (from-to)45-51
Number of pages7
JournalJournal of Surgical Research
Volume130
Issue number1
DOIs
StatePublished - Jan 1 2006

Keywords

  • Cytokines
  • Gene regulation
  • Inflammation
  • Liver regeneration
  • p53
  • Rodent
  • Transgenic/knockout
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Surgery

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