Sirt6 regulates autophagy in AGE-treated endothelial cells via KLF4.
Nutr Metab Cardiovasc Dis
; 32(3): 755-764, 2022 03.
Article
em En
| MEDLINE
| ID: mdl-35123854
ABSTRACT
BACKGROUND AND AIMS:
High glucose and its byproducts are important factors causing dysfunction of endothelial cells. Autophagy is critical for endothelial cellular homeostasis. However, the specific molecular mechanism of how autophagy is regulated in endothelial cells under high-glucose condition remains unknown. We aim to explore the role Sirt6 plays in regulating autophagy in AGE-treated endothelial cells and how this function is exerted via KLF4. METHODS ANDRESULTS:
Our results indicate that autophagy level increased in AGE-treated endothelial cells alongside with higher Sirt6 and KLF4 expression level. What's more, knock-in of Sirt6 by adenovirus led to augmented autophagy level while knockdown of Sirt6 led to the opposite. We also verified that Sirt6 affected KLF4 expression positively but KLF4 didn't influence Sirt6 expression level while knocking out of KLF4 impaired Sirt6-enhanced autophagy. Finally we found that STZ-induced diabetic mice showed more autophagosomes in endothelium and Sirt6 knockdown by adeno-associated virus reduced the number of autophagosomes. Knockdown of Sirt6 also caused impaired endothelium integrity but echocardiography indicated there were no significant functional differences.CONCLUSION:
Our research reveals more about how Sirt6 regulates autophagy in endothelial cells under high-glucose simulated condition and provides further insight into the relationships between Sirt6 and KLF4.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sirtuínas
/
Diabetes Mellitus Experimental
Limite:
Animals
Idioma:
En
Revista:
Nutr Metab Cardiovasc Dis
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
CIENCIAS DA NUTRICAO
/
METABOLISMO
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China