Lipid accumulation and transforming growth factor-beta upregulation in the kidneys of rats administered angiotensin II.
Abnormal lipid metabolism may play a role in progressive renal failure. We studied whether lipid accumulation occurs and whether lipid deposits are colocalized with transforming growth factor-beta1 (TGF-beta1) in the kidney of angiotensin II-infused animals. Oil red O staining showed marked lipid deposition in the tubular epithelial and vascular wall cells of angiotensin II-treated but not in norepinephrine-treated rats. Histological analyses showed that increased amounts of superoxide and intense TGF-beta1 mRNA expression were present in lipid-positive tubular epithelial cells in angiotensin II-infused animals. Protein expression of sterol regulatory element-binding protein 1 (SREBP-1) and mRNA expression of fatty acid synthase in the kidney were &3 times and 1.5 times, respectively, higher in angiotensin II-treated rats than in controls. Treatment of angiotensin II-infused animals with an iron chelator, deferoxamine, attenuated the angiotensin II-induced increases in renal expression of SREBP-1 and fatty acid synthase and normalized the lipid content in the renal cortical tissues. Abnormal lipid metabolism may be associated with upregulation of TGF-beta1 expression and aberrant iron homeostasis in the kidneys of angiotensin II-infused animals.
Saito
Kan
K
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Ishizaka
Nobukazu
N
Hara
Masumi
M
Matsuzaki
Gen
G
Sata
Masataka
M
Mori
Ichiro
I
Ohno
Minoru
M
Nagai
Ryozo
R
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000235:genetics; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D051780:Sterol Regulatory Element Binding Protein 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000187:drug effects*
D007502:Iron Chelating Agents; D008055:Lipids; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013481:Superoxides; D000804:Angiotensin II; D007501:Iron; D064429:Fatty Acid Synthases; D003676:Deferoxamine