Effect of KNDC1 overexpression on the senescence of human umbilical vein endothelial cells.
Mol Med Rep
; 17(5): 7037-7044, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29568929
ABSTRACT
Kinase non-catalytic C-lobe domain containing 1 (KNDC1) exists in dendrites, guanine nucleotide exchange factor complexes and neuronal cell bodies as a putative proteinprotein interaction module that regulates a number of signaling pathways. Previous studies have demonstrated that the knockdown of KNDC1 delays human umbilical vein endothelial cell (HUVEC) senescence. However, the effect of KNDC1 overexpression on HUVEC function remains unclear. In the present study, an adenovirus vector carrying KNDC1 was constructed and then transfected into endothelial cells to observe cell senescence. Furthermore, the effect of KNDC1 overexpression on HUVEC senescence was investigated in vitro and the underlying molecular mechanism was investigated. Senescenceassociated ßgalactosidase staining was used to determine cellular senescence and reactive oxygen species (ROS) were monitored to detect the level of cell oxidative stress. The mRNA transcription level and protein expression were analyzed by reverse transcriptionquantitative polymerase chain reaction and western blot analysis, respectively. The results demonstrated that KNDC1 overexpression possibly inhibited HUVEC activity and function and promoted HUVEC senescence. Mechanistic studies demonstrated that KNDC1 triggered a p53ROS positive feedback loop, which serves a crucial role in regulating senescence. In conclusion, to the best of the authors' knowledge, this is the first time that KNDC1adenovirus vector inhibition of HUVEC proliferation by activating the p53 signaling pathway has been reported. Theoretically, the results of the present study also support KNDC1 as a therapeutic target for future anti-senescence.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação para Cima
/
Senescência Celular
/
Fatores ras de Troca de Nucleotídeo Guanina
/
Células Endoteliais
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article