Hepatic changes of erythropoietin gene expression in a rat model of acute-phase response.
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.
Ramadori
Pierluigi
P
Division of Gastroenterology and Endocrinology, University Medical Center Göttingen, Göttingen, Germany.
Sheikh
Nadeem
N
Ahmad
Ghayyor
G
Dudas
Jozsef
J
Ramadori
Giuliano
G
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000210:Acute-Phase Reaction / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000097:blood / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012997:Solvents / Q000633:toxicity; D014425:Turpentine / Q000633:toxicity; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*; D000099162:Endothelial PAS Domain-Containing Protein 1
D000209:Acute-Phase Proteins; D051792:Basic Helix-Loop-Helix Proteins; D004921:Erythropoietin; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D012997:Solvents; D014425:Turpentine; D000099162:Endothelial PAS Domain-Containing Protein 1; C497444:Hif1a protein, rat