Bradykinin receptor 1 activation exacerbates experimental focal and segmental glomerulosclerosis

Bradykinin receptor 1 activation exacerbates experimental focal and segmental glomerulosclerosis

Author Pereira, Rafael L. Autor UNIFESP Google Scholar
Buscariollo, Bruna N. Autor UNIFESP Google Scholar
Correa-Costa, Matheus Google Scholar
Semedo, Patricia Autor UNIFESP Google Scholar
Oliveira, Cassiano D. Autor UNIFESP Google Scholar
Reis, Vanessa O. Autor UNIFESP Google Scholar
Maquigussa, Edgar Autor UNIFESP Google Scholar
Araujo, Ronaldo C. Autor UNIFESP Google Scholar
Braga, Tarcio T. Google Scholar
Soares, Maria Fernanda Sanches Autor UNIFESP Google Scholar
Moura, Ivan C. Google Scholar
Malheiros, Denise M. A. C. Google Scholar
Pacheco-Silva, Alvaro Autor UNIFESP Google Scholar
Keller, Alexandre C. Autor UNIFESP Google Scholar
Camara, Niels O. S. Autor UNIFESP Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Univ Paris 07
Hosp Israelita Albert Einstein
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
Keywords bradykinin B1 receptor
focal and segmental glomerulosclerosis
kinin
podocyte
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
INCT Complex Fluids
Grant number FAPESP: 04/08226-9
FAPESP: 07/07139-3
FAPESP: 2007/07120
FAPESP: 08/55125-4
CNPq: 501848/2009-6
Date 2011-06-01
Published in Kidney International. New York: Nature Publishing Group, v. 79, n. 11, p. 1217-1227, 2011.
ISSN 0085-2538 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent 1217-1227
Origin http://dx.doi.org/10.1038/ki.2011.14
Access rights Closed access
Type Article
Web of Science ID WOS:000290559400010
URI http://repositorio.unifesp.br/handle/11600/33770

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