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.
Division of Gastroenterology and Endocrinology, University Medical Center Göttingen, Göttingen, Germany.
Pierluigi
P
Ramadori
Nadeem
N
Sheikh
Ghayyor
G
Ahmad
Jozsef
J
Dudas
Giuliano
G
Ramadori
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