Trehalose promotes the survival of random-pattern skin flaps by TFEB mediated autophagy enhancement.
Cell Death Dis
; 10(7): 483, 2019 09 15.
Article
en En
| MEDLINE
| ID: mdl-31522191
ABSTRACT
Random-pattern skin flaps are commonly used and valuable tools in reconstructive surgery, however, post-operative random skin flap necrosis remains a major and common complication. Previous studies have suggested that activating autophagy, a major pathway for degradation of intracellular waste, may improve flap survival. In this study, we investigated whether trehalose, a novel and potent autophagy activator, improves random skin flap viability. Our results demonstrated that trehalose significantly improves viability, augments blood flow, and decreases tissue edema. Furthermore, we found that trehalose leads to increased angiogenesis, decreased apoptosis, and reduced oxidative stress. Using immunohistochestry and western blot, we demonstrated that trehalose augments autophagy, and that inhibition of autophagy augmentation using 3MA significantly blunted the aforementioned benefits of trehalose therapy. Mechanistically, we showed that trehalose's autophagy augmentation is mediated by activation and nuclear translocation of TFEB, which may be due to inhibition of Akt and activation of the AMPK-SKP2-CARM1 signaling pathway. Altogether, our results established that trehalose is a potent agent capable for significantly increasing random-pattern skin flap survival by augmenting autophagy and subsequently promoting angiogenesis, reducing oxidative stress, and inhibiting cell death.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piel
/
Autofagia
/
Colgajos Quirúrgicos
/
Trehalosa
/
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice
Límite:
Animals
Idioma:
En
Revista:
Cell Death Dis
Año:
2019
Tipo del documento:
Article
País de afiliación:
China