Knockout of receptor for advanced glycation ...
Document type :
Article dans une revue scientifique: Article original
DOI :
Title :
Knockout of receptor for advanced glycation end‐products attenuates age‐related renal lesions
Author(s) :
Teissier, Thibault [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Quersin, Valentine [Auteur]
Gnemmi, Viviane [Auteur]
Daroux, Maité [Auteur]
Centre Hospitalier Boulogne-sur-mer
Howsam, Michael [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Delguste, Florian [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lemoine, Cécile [Auteur]
Fradin, Chantal [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Schmidt, Ann‐marie [Auteur]
Cauffiez, Christelle [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Brousseau, Thierry [Auteur]
Glowacki, François [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Tessier, Frédéric [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Boulanger, Eric [Auteur]
Service de gériatrie
Frimat, Marie [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]

Lille Inflammation Research International Center - U 995 [LIRIC]
Quersin, Valentine [Auteur]
Gnemmi, Viviane [Auteur]

Daroux, Maité [Auteur]
Centre Hospitalier Boulogne-sur-mer
Howsam, Michael [Auteur]

Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Delguste, Florian [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lemoine, Cécile [Auteur]
Fradin, Chantal [Auteur]

Lille Inflammation Research International Center - U 995 [LIRIC]
Schmidt, Ann‐marie [Auteur]
Cauffiez, Christelle [Auteur]

Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Brousseau, Thierry [Auteur]

Glowacki, François [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Tessier, Frédéric [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Boulanger, Eric [Auteur]
Service de gériatrie
Frimat, Marie [Auteur]

Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Journal title :
Aging Cell
Publisher :
Wiley Open Access
Publication date :
2019-02-22
ISSN :
1474-9718
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Abstract Pro‐aging effects of endogenous advanced glycation end‐products (AGEs) have been reported, and there is increasing interest in the pro‐inflammatory and ‐fibrotic effects of their binding to RAGE (the main AGE ...
Show more >Abstract Pro‐aging effects of endogenous advanced glycation end‐products (AGEs) have been reported, and there is increasing interest in the pro‐inflammatory and ‐fibrotic effects of their binding to RAGE (the main AGE receptor). The role of dietary AGEs in aging remains ill‐defined, but the predominantly renal accumulation of dietary carboxymethyllysine (CML) suggests the kidneys may be particularly affected. We studied the impact of RAGE invalidation and a CML‐enriched diet on renal aging. Two‐month‐old male, wild‐type (WT) and RAGE −/− C57Bl/6 mice were fed a control or a CML‐enriched diet (200 μg CML/g food ) for 18 months. Compared to controls, we observed higher CML levels in the kidneys of both CML WT and CML RAGE −/− mice, with a predominantly tubular localization. The CML‐rich diet had no significant impact on the studied renal parameters, whereby only a trend to worsening glomerular sclerosis was detected. Irrespective of diet, RAGE −/− mice were significantly protected against nephrosclerosis lesions (hyalinosis, tubular atrophy, fibrosis and glomerular sclerosis) and renal senile apolipoprotein A‐II (ApoA‐II) amyloidosis ( p < 0.001). A positive linear correlation between sclerosis score and ApoA‐II amyloidosis score ( r = 0.92) was observed. Compared with old WT mice, old RAGE −/− mice exhibited lower expression of inflammation markers and activation of AKT, and greater expression of Sod2 and SIRT1. Overall, nephrosclerosis lesions and senile amyloidosis were significantly reduced in RAGE −/− mice, indicating a protective effect of RAGE deletion with respect to renal aging. This could be due to reduced inflammation and oxidative stress in RAGE −/− mice, suggesting RAGE is an important receptor in so‐called inflamm‐aging.Show less >
Show more >Abstract Pro‐aging effects of endogenous advanced glycation end‐products (AGEs) have been reported, and there is increasing interest in the pro‐inflammatory and ‐fibrotic effects of their binding to RAGE (the main AGE receptor). The role of dietary AGEs in aging remains ill‐defined, but the predominantly renal accumulation of dietary carboxymethyllysine (CML) suggests the kidneys may be particularly affected. We studied the impact of RAGE invalidation and a CML‐enriched diet on renal aging. Two‐month‐old male, wild‐type (WT) and RAGE −/− C57Bl/6 mice were fed a control or a CML‐enriched diet (200 μg CML/g food ) for 18 months. Compared to controls, we observed higher CML levels in the kidneys of both CML WT and CML RAGE −/− mice, with a predominantly tubular localization. The CML‐rich diet had no significant impact on the studied renal parameters, whereby only a trend to worsening glomerular sclerosis was detected. Irrespective of diet, RAGE −/− mice were significantly protected against nephrosclerosis lesions (hyalinosis, tubular atrophy, fibrosis and glomerular sclerosis) and renal senile apolipoprotein A‐II (ApoA‐II) amyloidosis ( p < 0.001). A positive linear correlation between sclerosis score and ApoA‐II amyloidosis score ( r = 0.92) was observed. Compared with old WT mice, old RAGE −/− mice exhibited lower expression of inflammation markers and activation of AKT, and greater expression of Sod2 and SIRT1. Overall, nephrosclerosis lesions and senile amyloidosis were significantly reduced in RAGE −/− mice, indicating a protective effect of RAGE deletion with respect to renal aging. This could be due to reduced inflammation and oxidative stress in RAGE −/− mice, suggesting RAGE is an important receptor in so‐called inflamm‐aging.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Collections :
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