Blockade of the kinin B1 receptor ameloriates glomerulonephritis.
Severe inflammation characterizes rapidly progressive glomerulonephritides, and expression of the kinin B1 receptor (B1R) associates with inflammation. Delayed B1R blockade reduces renal inflammation in a model of unilateral ureteral obstruction, but whether B1R modulates the pathophysiology of glomerulonephritides is unknown. Here, we observed an association of B1R protein expression and inflammation, in both glomeruli and the renal interstitium, in biopsies of patients with glomerulonephritides, Henoch-Schönlein purpura nephropathy, and ANCA-associated vasculitis. In the nephrotoxic serum-induced glomerulonephritis model, we observed upregulation of the B1R receptor; treatment with a B1R antagonist beginning 2 weeks after the onset of disease reduced both glomerular and tubular lesions and improved renal function. B1R blockade reduced renal chemokine expression and macrophage accumulation. Collectively, our data demonstrate that blockade of the kinin B1R has significant potential for the treatment of glomerulonephritis.
Klein
Julie
J
INSERM, U858/I2MR, Department of Renal and Cardiac Remodeling, Team 5, 31432 Toulouse Cedex 4, France.
Gonzalez
Julien
J
Decramer
Stéphane
S
Bandin
Flavio
F
Neau
Eric
E
Salant
David J
DJ
Heeringa
Peter
P
Pesquero
Joao-Bosco
JB
Schanstra
Joost-Peter
JP
Bascands
Jean-Loup
JL
D000818:Animals; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001706:Biopsy; D065169:Bradykinin B1 Receptor Antagonists; D018925:Chemokines / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004149:Dioxoles / Q000494:pharmacology; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D011695:IgA Vasculitis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism; D043783:Receptor, Bradykinin B1 / Q000378:metabolism; D012189:Retrospective Studies; D013449:Sulfonamides / Q000494:pharmacology
C487113:2-((3-(1,3-benzodioxol-5-yl)-3-(((6-methoxy-2-naphthyl)sulfonyl)amino)propanoyl)amino)-3-(4-((2,6-dimethylpiperidinyl)methyl)phenyl)-N-isopropyl-N-methylpropanamide; D065169:Bradykinin B1 Receptor Antagonists; D018925:Chemokines; D004149:Dioxoles; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D013449:Sulfonamides; D003404:Creatinine
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