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 Perez, Robert H. Pierce, Kenneth D. Chavin, Leonidas G. Koniaris

Research output: Contribution to journalArticle

47 Citations (Scopus)

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

Fingerprint

Growth Differentiation Factor 15
Tumor Necrosis Factor-alpha
Liver
Wounds and Injuries
Immediate-Early Genes
Tumor Necrosis Factor Receptors
Intraoperative Complications
Transforming Growth Factors
Liver Diseases
Hepatocytes
Shock
Hot Temperature

Keywords

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

ASJC Scopus subject areas

  • Surgery

Cite this

Growth differentiation factor-15 : Induction in liver injury through p53 and tumor necrosis factor-independent mechanisms. / Zimmers, Teresa A.; Jin, Xiaoling; Hsiao, Edward C.; Perez, Eduardo; Pierce, Robert H.; Chavin, Kenneth D.; Koniaris, Leonidas G.

In: Journal of Surgical Research, Vol. 130, No. 1, 01.01.2006, p. 45-51.

Research output: Contribution to journalArticle

Zimmers, Teresa A. ; Jin, Xiaoling ; Hsiao, Edward C. ; Perez, Eduardo ; Pierce, Robert H. ; Chavin, Kenneth D. ; Koniaris, Leonidas G. / Growth differentiation factor-15 : Induction in liver injury through p53 and tumor necrosis factor-independent mechanisms. In: Journal of Surgical Research. 2006 ; Vol. 130, No. 1. pp. 45-51.
@article{ade3f4e12716440c8f29d49413b21d5a,
title = "Growth differentiation factor-15: Induction in liver injury through p53 and tumor necrosis factor-independent mechanisms",
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.",
keywords = "Cytokines, Gene regulation, Inflammation, Liver regeneration, p53, Rodent, Transgenic/knockout, Tumor necrosis factor",
author = "Zimmers, {Teresa A.} and Xiaoling Jin and Hsiao, {Edward C.} and Eduardo Perez and Pierce, {Robert H.} and Chavin, {Kenneth D.} and Koniaris, {Leonidas G.}",
year = "2006",
month = "1",
day = "1",
doi = "10.1016/j.jss.2005.07.036",
language = "English",
volume = "130",
pages = "45--51",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Growth differentiation factor-15

T2 - Induction in liver injury through p53 and tumor necrosis factor-independent mechanisms

AU - Zimmers, Teresa A.

AU - Jin, Xiaoling

AU - Hsiao, Edward C.

AU - Perez, Eduardo

AU - Pierce, Robert H.

AU - Chavin, Kenneth D.

AU - Koniaris, Leonidas G.

PY - 2006/1/1

Y1 - 2006/1/1

N2 - 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.

AB - 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.

KW - Cytokines

KW - Gene regulation

KW - Inflammation

KW - Liver regeneration

KW - p53

KW - Rodent

KW - Transgenic/knockout

KW - Tumor necrosis factor

UR - http://www.scopus.com/inward/record.url?scp=29744437499&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=29744437499&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2005.07.036

DO - 10.1016/j.jss.2005.07.036

M3 - Article

C2 - 16154591

AN - SCOPUS:29744437499

VL - 130

SP - 45

EP - 51

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 1

ER -