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Prorenin receptor mediates inflammation in renal ischemia

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Clinical and Experimental Pharmacology and Physiology

Published online on

Abstract

We hypothesized that PRR contributes to renal inflammation in the 2‐kidney, 1‐clip (2K1C) renal ischemia model. Male Sprague‐Dawley rats were fed normal sodium diet. BP was obtained on day 0 and 28 after left renal artery clipping that reduced renal blood flow by 40%. Renal expression of TNF‐α, COX‐2, NF‐κB, IL‐1β, MCP‐1 and collagen type I were assessed in sham and 2K1C rats with or without left renal administration of scramble or PRR shRNA. At baseline, there were no differences in BP. Compared to sham, MAP significantly increased in clipped animals (sham: 102± 1.9 vs 2K1C: 131.8 ± 3.09 mmHg, P<0.05) and was not influenced by scramble or PRR shRNA treatment. Compared to sham and contra lateral (non‐clipped) kidney, there was upregulation in mRNA and protein expression of PRR (99% and 45%, P<0.01), TNF‐α (72% and 50%, P<0.05), COX‐2 (72% and 39%, P<0.05), p‐NF‐κB (92%, P<0.05), MCP‐1 (87%, P<0.05) and immunostaining of collagen type I in the clipped kidney. These increases were not influenced by scramble shRNA. Compared to 2K1C and scramble shRNA, PRR shRNA treatment in the clipped kidney significantly reduced the expression of PRR (62% and 57%, P<0.01), TNF‐α (51% and 50%, P<0.05), COX‐2 (50% and 56%, P<0.05), p‐NF‐κB by 68% (P<0.05), MCP‐1 by 73% (P<0.05) and collagen type I respectively. Ang II was increased in both kidneys and did not change in response to scramble or PRR shRNA treatments. We conclude that PRR mediates renal inflammation in renal ischemia independent of blood pressure and Ang II. This article is protected by copyright. All rights reserved.