Deletion of bradykinin B1 receptor reduces renal fibrosis

Author(s)

Wang‚ P.H.M. ; Cenedeze‚ M.A. ; Campanholle‚ G. ; Malheiros‚ D.M.A.C. ; de Moura Torres‚ H.A. ; Pesquero‚ J.B. ; Pacheco-Silva‚ A. ; C{\=a}mara‚ N.O.S.

• Document type: Journal article
• Source: International Immunopharmacology; v. 9, n. 6, p. 653-657, 2009.

Abstract

The Kallikrein-kinin system works through activation of two receptors. One constitutive, named B2 receptor (B2R) and another inducible, denominated 131 receptor (B1R). In renal fibrosis, B2R receptor activation appears to be protective, however B1R participation is unveiled. The aim of this study was to analyze how the deletion of the Ell R would modify tissue responses after unilateral ureteral obstruction (UUO). For that, B1R knockout (131 KO) and wild-type mice (B1B2WT) were subjected to UUO and sacrificed at days 1, 5 and 14. Renal dysfunction was assayed by urine proteinuria/creatinine ratio and percentage of tubulointerstitial fibrosis. Kidneys were harvested at day 5 to analyze anti and pro-inflammatory molecules expression by real-time PCR. We demonstrated that at all time points, B1KO mice presented lower proteinuria/creatinine ratio from bladder urine. Ell KO protection was reinforced by its lower tubular interstitial fibrosis percentage at day 14 (B1B2WT: 12.16 +/- 1.53% vs. B1KO: 6.73 +/- 1.07%, p<0.02). UUO was able to induce B1R expression and its highest transcription was achieved at day 5. At this day, B1KO had significant lower expression of proinflammatory molecules such as TGF-beta, MCP-1, OPN and IL-6 and higher anti-inflammatory components, as IL-10 and HO-1. Herein, we observed that Ell R deletion may be an important component in renal fibrosis prevention. (C) 2008 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 07/07139-3 - The role of heme oxygenase 1 in different renal inflammatory process in experimental animal models
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 06/03982-5 - Molecular aspects involved in leukocytes microbicidal and inflammatory activities in the lung
• Grantee: Sônia Jancar
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 04/08311-6 - Molecular, cellular and pathophysiological mechanisms on acute renal failure
• Grantee: Nestor Schor
• Support Opportunities: Research Projects - Thematic Grants