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In vivo bradykinin B2 receptor activation reduces renal fibrosis

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Item Type:Article
Title:In vivo bradykinin B2 receptor activation reduces renal fibrosis
Creators Name:Schanstra, J.P. and Neau, E. and Drogoz, P. and Gomez, M.A.A. and Novoa, J.M.L. and Calise, D. and Pecher, C. and Bader, M. and Girolami, J.P. and Bascands, J.L.
Abstract:Angiotensin-converting enzyme (ACE) inhibitors reduce the progression of various fibrotic renal diseases both in humans and in animal models. Unilateral ureteral obstruction (UUO) is an animal model of accelerated renal tubulointerstitial fibrosis that is attenuated by ACE inhibition. Although ACE inhibitors increase bradykinin concentrations in addition to their effect on angiotensin II formation, the role of bradykinin in renal fibrosis has not been studied. We show here that genetic ablation (B2(-/-) mice) or pharmacological blockade of the bradykinin B2 receptor increases UUO-induced interstitial fibrosis in mice, whereas transgenic rats expressing increased endogenous bradykinin show reduced UUO-induced interstitial fibrosis. The increased interstitial fibrosis in B2(-/-) mice was accompanied by a decreased activity of plasminogen activators (PAs) and metalloproteinase-2 (MMP-2), enzymes involved in ECM degradation, suggesting that the protective effects of bradykinin involve activation of a B2 receptor/PA/MMP-2 cascade. This ability of bradykinin to increase PA activity was confirmed in primary culture proximal tubular cells. Thus, in both mice and rats, bradykinin B2 receptor activation reduces renal tubulointerstitial fibrosis in vivo, most likely by increasing ECM degradation.
Keywords:Bradykinin, Cell Division, Collagen, Animal Disease Models, Extracellular Matrix, Extracellular Matrix Proteins, Fibrosis, Immunoenzyme Techniques, Kidney, Matrix Metalloproteinase, Inbred C57BL Mice, Knockout Mice, Interstitial Nephritis, Plasminogen Activators, Bradykinin B2 Receptor, Bradykinin Receptors, Tissue Kallikreins, Ureteral Obstruction, Animals, Mice, Rats
Source:Journal of Clinical Investigation
Publisher:American Society for Clinical Investigation
Page Range:371-379
Date:1 August 2002
Official Publication:https://doi.org/10.1172/JCI15493
PubMed:View item in PubMed

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