Bradykinin receptor 1 activation exacerbates experimental focal and segmental glomerulosclerosis
| Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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| Data(s) |
20/10/2012
20/10/2012
2011
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| Resumo |
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 FAPESP (Fundacao de Apoio a Pesquisa do Estado de Sao Paulo)[04/08226-9] Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) FAPESP (Fundacao de Apoio a Pesquisa do Estado de Sao Paulo)[07/07139-3] FAPESP (Fundacao de Apoio a Pesquisa do Estado de Sao Paulo)[2007/07120] Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Inserm Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) FAPESP/Inserm[08/55125-4] Inserm Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) International Associated Laboratory (CNPq/Inserm) INCT Complex Fluids Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) CNPq[501848/2009-6] |
| Identificador |
KIDNEY INTERNATIONAL, v.79, n.11, p.1217-1227, 2011 0085-2538 http://producao.usp.br/handle/BDPI/28331 10.1038/ki.2011.14 |
| Idioma(s) |
eng |
| Publicador |
NATURE PUBLISHING GROUP |
| Relação |
Kidney International |
| Direitos |
restrictedAccess Copyright NATURE PUBLISHING GROUP |
| Palavras-Chave | #bradykinin B1 receptor #focal and segmental glomerulosclerosis #kinin #podocyte #KININ B1 RECEPTOR #ENDOTOXIN-INDUCED INFLAMMATION #ISCHEMIA-REPERFUSION INJURY #CHRONIC RENAL-DISEASE #DOXORUBICIN NEPHROPATHY #GLOMERULAR PODOCYTES #B-1 RECEPTORS #KNOCKOUT MICE #GENE DELETION #B2 RECEPTORS #Urology & Nephrology |
| Tipo |
article original article publishedVersion |
