Promising therapeutic effect of thapsigargin nanoparticles on chronic kidney disease through the activation of Nrf2 and FoxO1.
Aging (Albany NY)
; 11(21): 9875-9892, 2019 11 12.
Article
em En
| MEDLINE
| ID: mdl-31714893
ABSTRACT
Pathophysiological states cause misfolded protein accumulation in the endoplasmic reticulum (ER). Then, ER stress and the unfolded protein response (UPR) are activated. Targeting ER stress may enhance the adaptive UPR and then protect the cell against pathogenic environments. In the present study, we utilized nanotechnology to synthesize thapsigargin nanoparticles (TG NPs) which induced ER stress and the UPR pathway, to study the role of ER stress and autophagy in chronic kidney disease (CKD). We found that the mRNA levels of ER stress- and autophagy-related molecules were elevated in the renal tissue of CKD patients compared to those of healthy individuals. Furthermore, TG NPs induced the UPR pathway and autophagy in HK-2 human kidney tubular epithelial cells. TG NPs protected HK-2 cells against oxidative stress-induced cell death through the activation of Nrf2 and FoxO1. The siRNA-mediated inhibition of Nrf2 or FoxO1 resulted in enhanced oxidative stress-induced cytotoxicity in HK-2 cells. In a mouse model of adenine diet-induced CKD, TG NPs and KIM-1-TG NPs ameliorated renal injury through the stimulation of ER stress and its downstream pathways. Our findings suggest that the induction of ER stress using pharmacological agents may offer a promising therapeutic strategy for preventing or interfering with CKD progression.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tapsigargina
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Insuficiência Renal Crônica
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Fator 2 Relacionado a NF-E2
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Nanopartículas
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Proteína Forkhead Box O1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article