Balance between the two kinin receptors in the progression of experimental focal and segmental glomerulosclerosis in mice

Balance between the two kinin receptors in the progression of experimental focal and segmental glomerulosclerosis in mice

Author Pereira, Rafael Luiz Autor UNIFESP Google Scholar
Felizardo, Raphael Jose Ferreira Autor UNIFESP Google Scholar
Cenedeze, Marcos Antonio Autor UNIFESP Google Scholar
Hiyane, Meire Ioshie Autor UNIFESP Google Scholar
Bassi, Enio Jose Autor UNIFESP Google Scholar
Amano, Mariane Tami Autor UNIFESP Google Scholar
Origassa, Clarice Sylvia Taemi Autor UNIFESP Google Scholar
Silva, Reinaldo Correia Autor UNIFESP Google Scholar
Aguiar, Cristhiane Favero Google Scholar
Carneiro, Sylvia Mendes Google Scholar
Pesquero, João Bosco Autor UNIFESP Google Scholar
Araujo, Ronaldo Carvalho Autor UNIFESP Google Scholar
Keller, Alexandre de Castro Autor UNIFESP Google Scholar
Monteiro, Renato C. Google Scholar
Moura, Ivan Cruz Google Scholar
Pacheco-Silva, Alvaro Autor UNIFESP Google Scholar
Camara, Niels Olsen Saraiva Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Inst Butantan
INSERM
Albert Einstein Hosp
Abstract Focal and segmental glomerulosclerosis (FSGS) is one of the most important renal diseases related to end-stage renal failure. Bradykinin has been implicated in the pathogenesis of renal inflammation, whereas the role of its receptor 2 (B2RBK; also known as BDKRB2) in FSGS has not been studied. FSGS was induced in wild-type and B2RBK-knockout mice by a single intravenous injection of Adriamycin (ADM). in order to further modulate the kinin receptors, the animals were also treated with the B2RBK antagonist HOE-140 and the B1RBK antagonist DALBK. Here, we show that the blockage of B2RBK with HOE-140 protects mice from the development of FSGS, including podocyte foot process effacement and the re-establishment of slit-diaphragm-related proteins. However, B2RBK-knockout mice were not protected from FSGS. These opposite results were due to B1RBK expression. B1RBK was upregulated after the injection of ADM and this upregulation was exacerbated in B2RBK-knockout animals. Furthermore, treatment with HOE-140 downregulated the B1RBK receptor. the blockage of B1RBK in B2RBK-knockout animals promoted FSGS regression, with a less-inflammatory phenotype. These results indicate a deleterious role of both kinin receptors in an FSGS model and suggest a possible cross-talk between them in the progression of disease.
Keywords Focal and segmental glomerulosclerosis
Bradykinin receptors
Inflammation
Podocyte
Fibrosis
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2012/05605-5
FAPESP: 07/07139-3
FAPESP: 12/02270-2
CNPq: 140739/2008-4
Date 2014-06-01
Published in Disease Models & Mechanisms. Cambridge: Company of Biologists Ltd, v. 7, n. 6, p. 701-710, 2014.
ISSN 1754-8403 (Sherpa/Romeo, impact factor)
Publisher Company of Biologists Ltd
Extent 701-710
Origin http://dx.doi.org/10.1242/dmm.014548
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000345002600011
URI http://repositorio.unifesp.br/handle/11600/37806

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