RAGE-mediated interstitial fibrosis in neonatal obstructive nephropathy is independent of NF-κB activation.
Kidney Int
; 84(5): 911-9, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-23677242
ABSTRACT
Urinary tract obstruction during nephron development causes tubular apoptosis, tubular atrophy, and interstitial fibrosis. Leukocyte recruitment is critical in the development of obstructive nephropathy leading to interstitial inflammation and renal fibrosis. RAGE, the receptor of advanced glycation end products, is implicated in chronic inflammation and has been recently identified as a novel receptor for the ß2-integrin Mac-1, cooperating with ICAM-1 and thereby directly mediating leukocyte recruitment in vivo. Here, we studied the role of RAGE and ICAM-1 in a model of unilateral ureteral obstruction in neonatal mice. Interestingly, the number of infiltrating leukocytes was independent of RAGE and ICAM-1 in the ureteral obstructed neonatal kidney. By contrast, galectin-3, a marker for profibrogenic M2 macrophages, was strongly reduced in ureteral obstructed RAGE and RAGE-Icam1 knockout mice. Snail expression and loss of E-cadherin but not NF-κB activation were attenuated in both knockout models. Epithelial cell cycle arrest at G2/M, which mediates kidney fibrosis, and transforming growth factor-ß expression were reduced in ureteral obstructed RAGE knockout mice. Thus, RAGE and ICAM-1 promote renal fibrosis in the developing kidney upon ureteral obstruction. Combined RAGE- and ICAM-1-blocking strategies may prove beneficial in neonatal obstructive nephropathy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Obstrução Ureteral
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Receptores Imunológicos
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NF-kappa B
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Células Epiteliais
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Rim
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Nefropatias
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Alemanha