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  • 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.

Disease models & mechanisms (2014-04-20)
Rafael Luiz Pereira, Raphael José Ferreira Felizardo, Marcos Antônio Cenedeze, Meire Ioshie Hiyane, Enio José Bassi, Mariane Tami Amano, Clarice Sylvia Taemi Origassa, Reinaldo Correia Silva, Cristhiane Fávero Aguiar, Sylvia Mendes Carneiro, João Bosco Pesquero, Ronaldo Carvalho Araújo, Alexandre de Castro Keller, Renato C Monteiro, Ivan Cruz Moura, Alvaro Pacheco-Silva, Niels Olsen Saraiva Câmara
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Doxorubicin hydrochloride, 98.0-102.0% (HPLC)
Sigma-Aldrich
Doxorubicin hydrochloride, suitable for fluorescence, 98.0-102.0% (HPLC)
Doxorubicin hydrochloride, European Pharmacopoeia (EP) Reference Standard
USP
Doxorubicin hydrochloride, United States Pharmacopeia (USP) Reference Standard