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This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/R1063    most recent 00281.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Ishizaka, N. Articles by Nagai, R. Search for Related Content PubMed PubMed Citation Articles by Ishizaka, N. Articles by Nagai, R.

APPETITE, OBESITY, DIGESTION, AND METABOLISM

Administration of ANG II induces iron deposition and upregulation of TGF-1 mRNA in the rat liver

Departments of ¹Cardiovascular Medicine, ²Nephrology, and ³Gastroenterology, University of Tokyo Graduate School of Medicine, Tokyo, Japan; ⁴Department of Gastroenterology and Hepatology, Saitama Medical School, Saitama, Japan; and ⁵Department of Pathology, Wakayama Medical College, Wakayama, Japan

Submitted 29 April 2004 ; accepted in final form 14 December 2004

We previously found that ANG II infusion into rats causes iron deposition in the kidney and heart, which may have a role in the regulation of profibrotic gene expression and tissue fibrosis. In the present study, we have investigated whether ANG II can also induce iron accumulation in the liver. Prussian blue staining detected frequent iron deposition in the interstitium of the liver of rats treated with pressor dose ANG II for 7 days, whereas iron deposition was absent in the livers of control rats. Immunohistochemical and histological analyses showed that some iron-positive nonparenchymal cells were positive for ferritin and heme oxygenase-1 (HO-1) protein and TGF-1 mRNA and were judged to be monocytes/macrophages. It was shown that ANG II infusion caused about a fourfold increase in ferritin and HO-1 protein expression by Western blot analysis and about a twofold increase in TGF-1 mRNA expression by Northern blot analysis, which were both suppressed by treating ANG II-infused rats with losartan and deferoxamine. In addition, mild interstitial fibrosis was observed in the liver of rats that had been treated with pressor dose ANG II for 7 days or with nonpressor dose ANG II for 30 days, the latter of which also caused loss of hepatocytes and intrahepatic hemorrhage in the liver. Taken together, our data suggest that ANG II infusion induces aberrant iron homeostasis in the liver, which may have a role in the ANG II-induced upregulation of profibrotic gene expression in the liver.

iron metabolism; oxidative stress; profibrotic gene; iron chelator

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