Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury

Teresa A. Zimmers, Xiaoling Jin, Edward C. Hsiao, Sharon A. McGrath, Aurora F. Esquela, Leonidas G. Koniaris

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

The immunoregulatory cytokine macrophage inhibitory cytokine-1 (MIC-1), a divergent TGF-β family member, and its murine ortholog, growth/differentiation factor-15 (GDF-15) are induced in hepatocytes by surgical and chemical injury and heat shock. To better understand the in vivo role this factor plays in organ injury, we examined the regulation of GDF-15 in murine models of kidney and lung injury. We demonstrate herein induction of GDF-15/MIC-1 after surgical, toxic/genotoxic, ischemic, and hyperoxic kidney or lung injury. Gdf15 induction was independent of protein synthesis, a hallmark of immediate-early gene regulation. Although TNF induced GDF-15 expression, injury-elicited Gdf15 expression was not reduced in mice deficient for both TNF receptor subtype. 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 after organ injury is a hallmark of many tissues. These data demonstrate that GDF-15/MIC-1 is an early mediator of the injury response in kidney and lung that might regulate inflammation, cell survival, proliferation, and apoptosis in a variety of injured tissues and disease processes.

Original languageEnglish (US)
Pages (from-to)543-548
Number of pages6
JournalShock
Volume23
Issue number6
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

Keywords

  • Cytokines
  • Gene regulation
  • Inflammation
  • Rodent
  • Transgenic/knockout

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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