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RAGE-mediated interstitial fibrosis in neonatal obstructive nephropathy is independent of NF-κB activation

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...

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Main Authors: Gasparitsch, Mojca (Author) , Arndt, Anne-Karin (Author) , Pawlitschek, Felix (Author) , Oberle, Stephan (Author) , Keller, Ursula (Author) , Kasper, Michael (Author) , Bierhaus, Angelika (Author) , Schaefer, Franz (Author) , Weber, Lutz T. (Author) , Lange-Sperandio, Bärbel (Author)
Format: Article (Journal)
Language:English
Published: 15 May 2013
In: Kidney international
Year: 2013, Volume: 84, Issue: 5, Pages: 911-919
ISSN:1523-1755
DOI:10.1038/ki.2013.171
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/ki.2013.171
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0085253815560560
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Author Notes:Mojca Gasparitsch, Anne-Karin Arndt, Felix Pawlitschek, Stephan Oberle, Ursula Keller, Michael Kasper, Angelika Bierhaus, Franz Schaefer, Lutz T. Weber and Bärbel Lange-Sperandio
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Summary: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 β2-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-β 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.
Item Description:Gesehen am 27.01.2020
Physical Description:Online Resource
ISSN:1523-1755
DOI:10.1038/ki.2013.171

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