Conséquences rénales de l’activation de la réponse UPR (Unfolded protein response) par des stress toxique et ischémique

Abstract : Native and grafted kidneys are stressed by multiple specific or non-specific insults leading to progressive structural deterioration. Responses to these insults are adaptive and preserve cell survival but may also promote inflammation, fibrosis and apoptosis. The most important of these adaptive pathways are HIF1α pathway, mTOR pathway, autophagy, unfolded protein response (UPR). The consequences of the UPR in kidney injuries are not well known. The objective of this study is to delineate the mechanisms and consequences of the activation of the UPR in response to toxic (cyclosporine) and ischemic (glucose starvation) stresses in two distinct cellular models (arterial endothelial cells and renal tubular cells). Here, we showed that UPR was engaged in cyclosporine-induced endothelial phenotypic changes, glucose starvation-induced inflammatory and angiogenic responses: NF-κB regulation by Ire1; distinct VEGF, bFGF and angiogenin regulation by Perk and Ire1. UPR is subtly modulated since its transducers do not induce identical processes. In conclusion these comprehensive works, we demonstrate the UPR is implicated in stress-induced adaptive pathways with different downstream responses according to the effector. Renal tissue degradation could be prevented by discovering and validating early biomarker and UPR modulators.
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Nicolas Bouvier. Conséquences rénales de l’activation de la réponse UPR (Unfolded protein response) par des stress toxique et ischémique. Médecine humaine et pathologie. Université René Descartes - Paris V, 2012. Français. ⟨NNT : 2012PA05P626⟩. ⟨tel-00793364⟩

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