title: Balance between the two kinin receptors in the progression of experimental focal and segmental glomerulosclerosis in mice.
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.
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, São Paulo 04023-900, Brazil. Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo 05508-000, Brazil.
authors.forename: Rafael Luiz
authors.initials: RL
authors.lastname: Pereira
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, São Paulo 04023-900, Brazil.
authors.forename: Raphael José Ferreira
authors.initials: RJ
authors.lastname: Felizardo
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, São Paulo 04023-900, Brazil.
authors.forename: Marcos Antônio
authors.initials: MA
authors.lastname: Cenedeze
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo 05508-000, Brazil.
authors.forename: Meire Ioshie
authors.initials: MI
authors.lastname: Hiyane
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, São Paulo 04023-900, Brazil.
authors.forename: Enio José
authors.initials: EJ
authors.lastname: Bassi
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, São Paulo 04023-900, Brazil.
authors.forename: Mariane Tami
authors.initials: MT
authors.lastname: Amano
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, São Paulo 04023-900, Brazil.
authors.forename: Clarice Sylvia Taemi
authors.initials: CS
authors.lastname: Origassa
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Translational Medicine Division, Federal University of São Paulo, São Paulo 04039-002, Brazil.
authors.forename: Reinaldo Correia
authors.initials: RC
authors.lastname: Silva
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo 05508-000, Brazil.
authors.forename: Cristhiane Fávero
authors.initials: CF
authors.lastname: Aguiar
authors.affiliation: Laboratory of Cellular Biology, Instituto Butantan, Av. Vital Brazil 1500, São Paulo 05503-900, Brazil.
authors.forename: Sylvia Mendes
authors.initials: SM
authors.lastname: Carneiro
authors.affiliation: Department of Biophysics, Federal University of São Paulo (UNIFESP), São Paulo 04023-062, Brazil.
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Pesquero
authors.affiliation: Department of Biophysics, Federal University of São Paulo (UNIFESP), São Paulo 04023-062, Brazil.
authors.forename: Ronaldo Carvalho
authors.initials: RC
authors.lastname: Araújo
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP), São Paulo 04023-062, Brazil.
authors.forename: Alexandre de Castro
authors.initials: Ade C
authors.lastname: Keller
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 699, Paris 75870, France.
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 699, Paris 75870, France.
authors.forename: Ivan Cruz
authors.initials: IC
authors.lastname: Moura
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, São Paulo 04023-900, Brazil. Instituto Israelita de Ensino e Pesquisa Albert Einstein, Renal Transplantation Unit, Albert Einstein Hospital, São Paulo 05521-000, Brazil.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pacheco-Silva
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, São Paulo 04023-900, Brazil. Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo 05508-000, Brazil. Niels@icb.usp.br.
authors.forename: Niels Olsen Saraiva
authors.initials: NO
authors.lastname: Câmara
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D018002:Receptors, Bradykinin; C065679:icatibant; D001920:Bradykinin
keywords: Bradykinin receptors; Fibrosis; Focal and segmental glomerulosclerosis; Inflammation; Podocyte
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