Excess iron into hepatocytes is required for activation of collagen type I gene during experimental siderosis.
OBJECTIVE
Liver fibrosis and cirrhosis represent common pathological findings in humans with iron overload. This study was undertaken to assess whether in vivo targeting of iron to liver parenchymal or nonparenchymal cells would differently affect collagen gene activity.


METHODS
Rats were treated with an iron diet or intramuscular injections of iron dextran, and in situ hybridization analyses on liver samples were performed.


RESULTS
These iron treatments determined parenchymal or reticuloendothelial cell iron overload, respectively. The typical distribution of iron into different liver cells was documented by histochemistry and confirmed by in situ hybridization analysis with a ferritin L complementary RNA probe. In iron-fed rats, in situ hybridization analysis identified a signal for collagen type I messenger RNA into nonparenchymal cells in zones I and II. In rats with nonparenchymal cell iron overload, no activation of collagen gene expression was detected into or near iron-laden nonparenchymal cells. These findings were also confirmed by quantitative Northern blot analysis.


CONCLUSIONS
The results of this study indicate that, regardless of the total hepatic iron burden, selective localization of iron into liver cells (i.e., parenchymal cells) is required for the activation of collagen gene during long-term iron overload in rodents.
Gualdi
R
R
Department of Internal Medicine, University of Modena, Italy.
Casalgrandi
G
G
Montosi
G
G
Ventura
E
E
Pietrangelo
A
A
D000818:Animals; D003094:Collagen / Q000235:genetics*; D005786:Gene Expression Regulation; D006651:Histocytochemistry; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012806:Siderosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D014018:Tissue Distribution
D012333:RNA, Messenger; D003094:Collagen; D007501:Iron