Titre :

Kidney diseases and Endothelium:RAGE (receptor for advanced glycation end products): from inflammation to aging

Titre en anglais :

Kidney diseases and Endothelium:RAGE (receptor for advanced glycation end products): from inflammation to aging

Auteur(s) :

Frimat, Marie [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]

Directeur(s) de thèse :

Pr Marc HAZZAN

Date de soutenance :

2021-02-09

Organisme de délivrance :

UNIVERSITE LILLE 2 - FACULTE DE MEDECINE H. WAREMBOURG
EDBSL (lille2)

Mot(s)-clé(s) :

Maladie rénale
endothelium
complement
RAGE
vieillissement

Mot(s)-clé(s) en anglais :

Kidney disease
endothelium
complement
RAGE
aging

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Our current understanding of the receptor for advanced glycation end products, RAGE, relies heavily upon research about its interactions with AGEs (advanced glycation products, after which it is named), especially in ...
Lire la suite >Our current understanding of the receptor for advanced glycation end products, RAGE, relies heavily upon research about its interactions with AGEs (advanced glycation products, after which it is named), especially in diabetes mellitus. RAGE is more broadly involved in both immunity and inflammation with more than 28 known ligands including many PAMPs (pathogen associated molecular pattern) and DAMPs (danger associated molecular pattern), leading it to be considered as a pattern recognition receptor. In mice, RAGE deletion has been shown to be protective against cardiovascular and Alzheimer’s diseases and, as our team has recently shown, against renal ageing. Thus, we hypothesize this receptor could be a driver of ageing ("inflammaging") through its pro-inflammatory, -oxidative, -apoptotic, -fibrotic effects, opening up significant possibilities in the development of anti-RAGE therapeutics.Many questions remain, however: to what extent do the different RAGE ligands compete for binding, and how does this competition modulate its activation? Are the activated signalling pathways ligand-specific, tissue-specific or perhaps specific to the configuration of RAGE in its homodimeric, oligomeric or proposed heterodimeric (e.g. with TLRs) forms? Is RAGE an actor for the heterogeneity of clinical diseases expression, especially vascular pathologies? Could it be a potential therapeutic target in these pathologies?From models of vascular or renal diseases for which we have privileged access to data or samples from constituted patient cohorts (thrombotic microangiopathies, TMA; antipholipid syndrome, APLS; vasculopathies related to chronic renal failure), we will continue to study the mechanisms of endothelial activation and acceleration of ageing and will focus on the role of RAGE in these processes. We will study the relationships between RAGE and other receptors of innate immunity, such as TLRs and will define to what extent these potential interactions modulate the downstream impact on intracellular signalling and their pro-inflammatory consequences. Having recently identified haem, a product of haemolysis, as a ligand to RAGE, we will analyse whether, like the complement and heme-oxygenase systems, RAGE is involved in the susceptibility of some vascular beds to damage in haemolytic conditions. We will also investigate whether the pharmacological inhibition of RAGE reduce the inflammatory response or whether this is compensated by the activation of other receptors. The objective of this project will therefore be to improve our understanding of the mechanisms involving RAGE in endothelial activation and leading to premature vascular and renal ageing through inflammatory and oxidative processes. We thus hope to participate in deciphering the role of RAGE in ageing and to understand how to advantageously modulate its activation for successful ageingLire moins >

Langue :

Français

Collections :

• Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167

Source :

Harvested from HAL