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Title: Bradykinin receptor 1 activation exacerbates experimental focal and segmental glomerulosclerosis
Authors: Pereira, Rafael L. [UNIFESP]
Buscariollo, Bruna N. [UNIFESP]
Correa-Costa, Matheus
Semedo, Patricia [UNIFESP]
Oliveira, Cassiano D. [UNIFESP]
Reis, Vanessa O. [UNIFESP]
Maquigussa, Edgar [UNIFESP]
Araujo, Ronaldo C. [UNIFESP]
Braga, Tarcio T.
Soares, Maria Fernanda Sanches [UNIFESP]
Moura, Ivan C.
Malheiros, Denise M. A. C.
Pacheco-Silva, Alvaro [UNIFESP]
Keller, Alexandre C. [UNIFESP]
Camara, Niels O. S. [UNIFESP]
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Univ Paris 07
Hosp Israelita Albert Einstein
Keywords: bradykinin B1 receptor
focal and segmental glomerulosclerosis
Issue Date: 1-Jun-2011
Publisher: Nature Publishing Group
Citation: Kidney International. New York: Nature Publishing Group, v. 79, n. 11, p. 1217-1227, 2011.
Abstract: 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 2011
ISSN: 0085-2538
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