Hepatic changes of erythropoietin gene expression in a rat model of acute-phase response

Liver Int. 2010 Jan;30(1):55-64. doi: 10.1111/j.1478-3231.2009.02131.x. Epub 2009 Oct 13.

Abstract

An acute-phase response is the systemic reaction of an organism to insult (e.g. infection, trauma and burning). It represents the 'first line' of defence of the body to tissue-damaging attacks. In the present work, we used a rat model of an intra-muscular turpentine oil (TO) injection to analyse erythropoietin (EPO) gene expression changes in the liver, one of the main target organs of acute-phase cytokines. EPO began to increase in the serum of TO-treated animals 6 h after injection and reached a maximum at 24 h (125+/-20 pg/ml). The detection of total RNA by polymerase chain reaction analysis showed that the levels of EPO gene expression in the liver were considerably increased between 2 and 12 h by up to 20-fold at the peak after TO administration, followed by a gradual decrease over the next 48 h, although the values remained significantly higher compared with the control group. In the kidney, after a sudden slight increase, the values declined progressively to 3.5-fold decrease at 12 h after the injection. In the liver, a parallel upregulation of the hypoxia-inducible factor-1 (HIF-1) alpha gene was observed (up to 4.7-fold increase), while HIF-2 alpha gene expression remained unaltered. On the other hand, the protein of both genes became detectable after the injection and increased progressively over 24 h, with a subsequent decline. These results suggest that EPO may be added to the increasing group of positive acute-phase proteins and the liver might represent the major source of the hormone under these conditions in the rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism
  • Acute-Phase Reaction / chemically induced
  • Acute-Phase Reaction / genetics*
  • Acute-Phase Reaction / metabolism
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Disease Models, Animal
  • Erythropoietin / blood
  • Erythropoietin / genetics*
  • Gene Expression / physiology*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Kidney / drug effects
  • Liver / drug effects
  • Liver / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Solvents / toxicity
  • Turpentine / toxicity
  • Up-Regulation / drug effects
  • Up-Regulation / genetics*

Substances

  • Acute-Phase Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • Solvents
  • Erythropoietin
  • endothelial PAS domain-containing protein 1
  • Turpentine