Bradykinin receptor 1 activation exacerbates experimental focal and segmental glomerulosclerosis

Focal and segmental glomerulosclerosis (FSGS) is one of the most important causes of end-stage renal failure. the bradykinin B1 receptor has been associated with tissue inflammation and renal fibrosis. To test for a role of the bradykinin B1 receptor in podocyte injury, we pharmacologically modulated its activity at different time points in an adriamycin-induced mouse model of FSGS. Estimated albuminuria and urinary protein to creatinine ratios correlated with podocytopathy. Adriamycin injection led to loss of body weight, proteinuria, and upregulation of B1 receptor mRNA. Early treatment with a B1 antagonist reduced albuminuria and glomerulosclerosis, and inhibited the adriamycin-induced downregulation of podocin, nephrin, and alpha-actinin-4 expression. Moreover, delayed treatment with antagonist also induced podocyte protection. Conversely, a B1 agonist aggravated renal dysfunction and even further suppressed the levels of podocyte-related molecules. Thus, we propose that kinin has a crucial role in the pathogenesis of FSGS operating through bradykinin B1 receptor signaling. Kidney International (2011) 79, 1217-1227; doi:10.1038/ki.2011.14; published online 16 March 2011Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)INCT Complex FluidsUniv São Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Imunobiol Transplante, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Nefrol, Dept Med, Lab Imunol Clin & Expt, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Nefrol, Dept Med, Mol Biol Lab, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Patol, BR-04023900 São Paulo, BrazilUniv Paris 07, INSERM, U699, Paris, FranceUniv São Paulo, Dept Patol, BR-05508900 São Paulo, BrazilHosp Israelita Albert Einstein, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Nefrol, Dept Med, Lab Imunol Clin & Expt, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Nefrol, Dept Med, Mol Biol Lab, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Patol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023900 São Paulo, BrazilFAPESP: 04/08226-9FAPESP: 07/07139-3FAPESP: 2007/07120FAPESP: 08/55125-4CNPq: 501848/2009-6Web of Scienc