Delayed blockade of the kinin B1 receptor reduces renal inflammation and fibrosis in obstructive nephropathy

Renal fibrosis is the common histological feature of advanced glomerular and tubulointerstitial disease leading to end-stage renal disease (ESRD). However, specific antifibrotic therapies to slow down the evolution to ESRD are still absent. Because persistent inflammation is a key event in the development of fibrosis, we hypothesized that the proinflammatory kinin B1 receptor (B1R) could be such a new target. Here we show that, in the unilateral ureteral obstruction model of renal fibrosis, the B1R is overexpressed and that delayed treatment with an orally active non-peptide B1R antagonist blocks macrophage infiltration, leading to a reversal of the level of renal fibrosis. in vivo bone marrow transplantation studies as well as in vitro studies on renal cells show that part of this antifibrotic mechanism of B1R blockade involves a direct effect on resident renal cells by inhibiting chemokine CCL2 and CCL7 expression. These findings suggest that blocking the B1R is a promising antifibrotic therapy.-Klein, J., Gonzalez, J., Duchene, J., Esposito, L., Pradere, J. P., Neau, E., Delage, C., Calise, D., Ahluwalia, A., Carayon, P., Pesquero, J. B., Bader, M., Schanstra, J. P., Bascands, J. L. Delayed blockade of the kinin B1 receptor reduces renal inflammation and fibrosis in obstructive nephropathy. FASEB J. 23, 134-142 (2009)INSERMUniversite Toulouse III Paul SabatierSanofi-AventisBasic Science Fellowship of the Barts and the London CharityINSERM, Dept Renal, F-31432 Toulouse, FranceINSERM, Cardiac Remodeling Team 5, F-31432 Toulouse, FranceUniv Toulouse 3, F-31062 Toulouse, FranceBarts & London Med Sch, William Harvey Res Inst, London, EnglandToulouse Univ Hosp, Nephrol & Kidney Transplantat Dept, CHU Rangueil, Toulouse, FranceINSERM, Zootechny Dept Expt Microsurg, Toulouse, FranceSanofi Aventis R&D, Montpellier, FranceUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, BrazilMax Delbruck Ctr Mol Med, Berlin, GermanyUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, BrazilWeb of Scienc

A nest in renal fibrosis?

Sakairi and collaborators show that some tubular cells as well as some interstitial myofibroblasts express the intermediate filament protein nestin. These findings evoke questions about the origin and role of these nestin-positive cells in the development of tubulointerstitial fibrosis