Deletion of bradykinin B1 receptor reduces renal fibrosis.
The Kallikrein-kinin system works through activation of two receptors. One constitutive, named B2 receptor (B2R) and another inducible, denominated B1 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 B1R would modify tissue responses after unilateral ureteral obstruction (UUO). For that, B1R knockout (B1KO) 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. B1KO 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 pro-inflammatory 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 B1R deletion may be an important component in renal fibrosis prevention.
Wang
Pamella Huey Mei
PH
Laboratório de Imunologia Clínica e Experimental, Division of Nephrology, Universidade Federal de São Paulo, São Paulo, Brazil.
Cenedeze
Marcos Antonio
MA
Campanholle
Gabriela
G
Malheiros
Denise Maria Avancini Costa
DM
Torres
Hugo Arruda de Moura
HA
Pesquero
João Bosco
JB
Pacheco-Silva
Alvaro
A
Câmara
Niels Olsen Saraiva
NO
D000818:Animals; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism; D003404:Creatinine / Q000097:blood / Q000652:urine; D005355:Fibrosis; D017353:Gene Deletion; D051547:Heme Oxygenase-1 / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D016234:Kallikrein-Kinin System / Q000235:genetics; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011507:Proteinuria / Q000652:urine; D043783:Receptor, Bradykinin B1 / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D043783:Receptor, Bradykinin B1; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D003404:Creatinine; D051547:Heme Oxygenase-1