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

Autor(es):Mostrar menos -

Pereira, Rafael Luiz ^{[1, 2]} ; Ferreira Felizardo, Raphael Jose ^[2] ; Cenedeze, Marcos Antoino ^[2] ; Hiyane, Meire Ioshie ^[1] ; Bassi, Enio Jose ^[2] ; Amano, Mariane Tami ^[2] ; Taemi Origassa, Clarice Sylvia ^[2] ; Silva, Reinaldo Correia ^[3] ; Aguiar, Cristhiane Favero ^[1] ; Carneiro, Sylvia Mendes ^[4] ; Pesquero, Joao Bosco ^[5] ; Araujo, Ronaldo Carvalho ^[5] ; Keller, Alexandre de Castro ^[6] ; Monteiro, Renato C. ^[7] ; Moura, Ivan Cruz ^[7] ; Pacheco-Silva, Alvaro ^{[2, 8]} ; Saraiva Camara, Niels Olsen ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, BR-05508000 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Clin & Expt Immunol Lab, Div Nephrol, BR-04023900 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Translat Med Div, Clin & Expt Immunol Lab, BR-04039002 Sao Paulo - Brazil

^[4] Inst Butantan, Lab Cellular Biol, BR-05503900 Sao Paulo - Brazil

^[5] Fed Univ Sao Paulo UNIFESP, Dept Biophys, BR-04023062 Sao Paulo - Brazil

^[6] Fed Univ Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, BR-04023062 Sao Paulo - Brazil

^[7] INSERM, Unite Mixte Rech 699, F-75870 Paris - France

^[8] Albert Einstein Hosp, Inst Israelita Ensino & Pesquisa Albert Einst, Renal Transplantat Unit, BR-05521000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Disease Models & Mechanisms; v. 7, n. 6, p. 701-710, JUN 2014.
• Citações Web of Science: 6

Resumo

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. (AU)

• Processo FAPESP: 07/07139-3 - Investigando o papel da heme-oxigenase 1 em diferentes processos inflamatórios renais em modelos animais
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/02270-2 - Novos mecanismos celulares, moleculares e imunológicos das lesões renais agudas e crônicas: busca por novas estratégias terapêuticas
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/05605-5 - Sinalização via mTOR na modulação da atividade de macrófagos na progressão da glomeruloesclerose segmentar e focal.
• Beneficiário: Rafael Luiz Pereira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado