Melatonin activates ABCA1 via the BiP/NRF1 pathway to suppress high-cholesterol-induced apoptosis of mesenchymal stem cells.
Stem Cell Res Ther
; 12(1): 114, 2021 02 05.
Article
en En
| MEDLINE
| ID: mdl-33546749
ABSTRACT
BACKGROUND:
Retarded wound healing in patients with obesity contributes to a risk of complications associated with vascular insufficiency and oxidative stress. The high cholesterol levels of patients with obesity are associated with apoptosis of engrafted umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs). Melatonin contributes to the prevention of cholesterol accumulation in patients with obesity via a mechanism that is poorly understood. We therefore investigated the regulatory mechanism of melatonin in cholesterol-induced apoptosis.METHODS:
The protective effects of melatonin on cholesterol-induced apoptosis were investigated in UCB-MSCs. We used a mouse model of induced obesity to show that melatonin treatment restored the survival rate of transplanted UCB-MSCs and their wound-healing capacity. The mean values of the treatment groups were compared with those of the control group using Student's t test, and differences among three or more groups were analyzed using one-way analysis of variance with Dunnett's multiple comparison test.RESULTS:
Melatonin treatment increased the expression of ATP-binding cassette subfamily A member 1 (ABCA1), which reduced cholesterol accumulation and cholesterol-induced apoptosis. The mouse skin wound healing model showed that melatonin treatment restored the survival rate of transplanted UCB-MSCs and the wound-healing capacity of obese mice. Melatonin inhibited the expression of binding immunoglobulin protein (BiP) through the regulation of MT2/Sp1-dependent microRNA-597-5p. Melatonin decreased the co-localization of BiP with nuclear factor erythroid 2-related factor 1 (NRF1), which resulted in increased ABCA1 expression.CONCLUSION:
Melatonin induced the efflux of intracellular cholesterol through ABCA1 to decrease apoptosis of UCB-MSCs via an MT2-dependent BiP/NRF1 pathway.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trasplante de Células Madre Mesenquimatosas
/
Células Madre Mesenquimatosas
/
Hipercolesterolemia
/
Melatonina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Stem Cell Res Ther
Año:
2021
Tipo del documento:
Article