著者

Kan SAITO Nobukazu ISHIZAKA Toru AIZAWA Masataka SATA Naoyuki ISO-O Eisei NOIRI Minoru OHNO Ryozo NAGAI

出版者

The Japanese Society of Hypertension

雑誌

Hypertension Research (ISSN:09169636)

巻号頁・発行日

vol.27, no.8, pp.599-607, 2004 (Released:2004-10-19)

参考文献数

30

被引用文献数

18 27

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We have previously shown that abnormal iron metabolism might be one underlying mechanism of the renal damage observed in the angiotensin II-infused rat. Transforming growth factor-β1 (TGF-β1) is known to play a crucial role in the development of renal damage induced by activation of the renin-angiotensin-aldosterone system. The purpose of the present study was to examine the effects of an iron chelator and a free radical scavenger on the angiotensin II-induced upregulation of TGF-β1 in the kidney. Rats were given angiotensin II (0.7 mg/kg/day) via osmotic minipumps for 7 days. The expressions of the mRNAs of TGF-β1 and collagen types I and IV were significantly increased in response to angiotensin II treatment. Histologic analysis showed that TGF-β1 expression was upregulated mainly in tubular epithelial cells, and occasionally in glomerular and perivascular cells, some of which were identified as monocytes and/or macrophages. Although tubular cells that overexpressed TGF-β1 did not contain iron particles, angiotensin II-induced TGF-β1 upregulation was suppressed by the iron chelator and the free radical scavenger. The free radical scavenger also suppressed angiotensin II-induced upregulation of heme oxygenase-1, an oxidative-stress sensitive gene. By contrast, administration of iron dextran to rats induced upregulation of TGF-β1 mRNA. Collectively, these data suggest that the renal iron overload and presumed subsequent increase in oxidative stress play a role in angiotensin II-induced upregulation of the mRNAs of TGF-β1 and collagen types I and IV in the kidney. (Hypertens Res 2004; 27: 599-607)