RGD Reference Report - RAGE-mediated interstitial fibrosis in neonatal obstructive nephropathy is independent of NF-kappaB activation. - Rat Genome Database

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

Authors: Gasparitsch, M  Arndt, AK  Pawlitschek, F  Oberle, S  Keller, U  Kasper, M  Bierhaus, A  Schaefer, F  Weber, LT  Lange-Sperandio, B 
Citation: Gasparitsch M, etal., Kidney Int. 2013 May 15. doi: 10.1038/ki.2013.171.
RGD ID: 7243949
Pubmed: PMID:23677242   (View Abstract at PubMed)
DOI: DOI:10.1038/ki.2013.171   (Journal Full-text)

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 beta2-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-kappaB activation were attenuated in both knockout models. Epithelial cell cycle arrest at G2/M, which mediates kidney fibrosis, and transforming growth factor-beta 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.Kidney International advance online publication, 15 May 2013; doi:10.1038/ki.2013.171.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ureteral obstruction  ISOAger (Mus musculus)7243949; 7243949 RGD 
ureteral obstruction  IMP 7243949 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ager  (advanced glycosylation end product-specific receptor)

Genes (Mus musculus)
Ager  (advanced glycosylation end product-specific receptor)

Genes (Homo sapiens)
AGER  (advanced glycosylation end-product specific receptor)


Additional Information