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1 Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Okayama, Japan
2 Division of Nephrology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan
3 Department of Medicine II, Kansai Medical School, Osaka, Osaka, Japan
* To whom correspondence should be addressed. E-mail: yyasushi{at}md.okayama-u.ac.jp.
Angiotensin II mediates the progression of renal disease through type 1 receptor (AT1R). Recent studies have suggested that type 2 receptor (AT2R)-mediated signaling inhibits cell proliferation by counteracting the actions of AT1R. The aim of the present study was to determine the effect of AT2R overexpression on glomerular injury induced by 5/6 nephrectomy (5/6Nx). AT2 receptor transgenic mice (AT2-Tg), overexpressing AT2R under the control of 
-smooth muscle actin (-SMA) promoter, and control wild type mice (Wild), were subjected to 5/6Nx. In AT2-Tg, the glomerular expression of ... was up-regulated after 5/6Nx. Urinary albumin excretion at 12 weeks after 5/6Nx was decreased by 33.7% in AT2-Tg as compared to Wild. Glomerular size in AT2-Tg was significantly smaller than in Wild after 5/6Nx (93.1 ± 3.0 vs. 103.3 ± 1.8 µm; P<0.05). Immunohistochemistry revealed significant decreases in glomerular expression of platelet-derived
growth factor-BB chain (PDGF-BB) and transforming growth factor 
1 (TGF-1) in AT2-Tg with
5/6Nx as compared to Wild. Urinary excretion of nitric oxide metabolites was increased in AT2-Tg by 2.5-fold as compared to Wild. Electrophoretic mobility-shift assay showed that activation of early growth response gene-1 (Egr-1), which induces the transcription of PDGF-BB and TGF-1, was decreased in AT2-Tg. These changes in AT2-Tg at 12 weeks after 5/6Nx were blocked by the AT2R antagonist, PD123319. Taken together, our findings suggest that AT2R-mediated signaling may protect from glomerular injuries induced by 5/6Nx and that overexpression of AT2R may serve as a potential therapeutic strategy for glomerular disorders.
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