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

• Autor(a) principal: Pereira, Rafael Luiz [UNIFESP]
• Data de Publicação: 2014
• Outros Autores: Felizardo, Raphael Jose Ferreira [UNIFESP], Cenedeze, Marcos Antonio [UNIFESP], Hiyane, Meire Ioshie [UNIFESP], Bassi, Enio Jose [UNIFESP], Amano, Mariane Tami [UNIFESP], Origassa, Clarice Sylvia Taemi [UNIFESP], Silva, Reinaldo Correia [UNIFESP], Aguiar, Cristhiane Favero, Carneiro, Sylvia Mendes, Pesquero, João Bosco [UNIFESP], Araujo, Ronaldo Carvalho [UNIFESP], Keller, Alexandre de Castro [UNIFESP], Monteiro, Renato C., Moura, Ivan Cruz, Pacheco-Silva, Alvaro [UNIFESP], Camara, Niels Olsen Saraiva [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1242/dmm.014548; http://repositorio.unifesp.br/handle/11600/37806
• topic: Focal and segmental glomerulosclerosis; Bradykinin receptors; Inflammation; Podocyte; Fibrosis

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.