4-Octyl itaconate protects against renal fibrosis via inhibiting TGF-ß/Smad pathway, autophagy and reducing generation of reactive oxygen species.
Eur J Pharmacol
; 873: 172989, 2020 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-32032597
Renal fibrosis is an inevitable course of all kinds of progressive chronic kidney disease (CKD). Itaconic acid is an endogenous metabolite that has shown anti-inflammatory and antioxidant effects. 4-octyl itaconate (OI), a derivative of itaconic acid with higher fat solubility, can penetrate the cell membranes and be metabolized into itaconic acid in vitro. However, whether OI has an anti-renal fibrotic effect is still unclear. The current study purposed to investigate the anti-fibrotic effect in renal and the underlying mechanisms of OI. The unilateral ureteral occlusion (UUO) model and adenine-induced fibrosis model in Sprague-Dawley (SD) rats and Transforming growth factor-ß1 (TGF-ß1) induced HK-2 cells were applied to investigate the renoprotective effects of OI. This study reports for the first time that OI ameliorated renal fibrosis by suppressing the activation of TGF-ß/Smad and nuclear factor kappa B (NF-κB) pathways, reducing generation of reactive oxygen species and inhibiting autophagy. These results clearly suggest that OI has great clinical potential for managing renal fibrosis.
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MEDLINE
Assunto principal:
Autofagia
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Succinatos
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Transdução de Sinais
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Fator de Crescimento Transformador beta
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Espécies Reativas de Oxigênio
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Substâncias Protetoras
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Proteínas Smad
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Nefropatias
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Antioxidantes
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article