Angiotensin II-induced regulation of the expression and localization of iron metabolism-related genes in the rat kidney.
Due to recent discoveries of novel genes involved in iron metabolism, our understanding of the molecular mechanisms underlying iron metabolism has dramatically increased. We have previously shown that the administration of angiotensin II alters iron homeostasis in the rat kidney, which may in turn aggravate angiotensin II-induced renal damage. Here we have investigated the effect of angiotensin II administration on the localization and expression of transferrin receptor (TfR), divalent metal transporter 1 (DMT1), ferroportin 1 (FPN), and hepcidin mRNA in the rat kidney. Weak expression of TfR, DMT1, FPN, and hepcidin mRNA was observed in the kidneys of control rats. In contrast, after 7 days of angiotensin II infusion by osmotic minipump, the expression of these mRNAs was more widely distributed. Staining of serial sections revealed that some, but not all, of the renal tubular cells positive for these genes contained iron deposits in the kidney of angiotensin II-infused animals. Real-time polymerase chain reaction (PCR) showed that the mRNA expression of TfR, iron-responsive element-negative DMT1, FPN, and hepcidin mRNA increased ~1.9-fold, ~1.7-fold, ~2.3-fold, and ~4.7-fold, respectively, after angiotensin II infusion as compared with that of untreated controls, and that these increases could be suppressed by the concomitant administration of losartan. Our data demonstrate that these genes were unequivocally expressed in the kidney and could be regulated by angiotensin II infusion. The relative contribution, if any, of these genes to renal and/or whole-body iron homeostasis in various disorders in which the renin angiotensin system is activated should be investigated in future studies.
Ishizaka
Nobukazu
N
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Japan. nobuishizka-tky@umin.ac.jp
Saito
Kan
K
Furuta
Kyoko
K
Matsuzaki
Gen
G
Koike
Kazuhiko
K
Noiri
Eisei
E
Nagai
Ryozo
R
D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D064451:Hepcidins; D007501:Iron / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011990:Receptors, Transferrin / Q000235:genetics*; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D000804:Angiotensin II; D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D064451:Hepcidins; D007501:Iron; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C578703:Hamp protein, rat