Thymoquinone suppresses platelet-derived growth factor-BB-induced vascular smooth muscle cell proliferation, migration and neointimal formation.
J Cell Mol Med
; 23(12): 8482-8492, 2019 12.
Article
en En
| MEDLINE
| ID: mdl-31638340
ABSTRACT
The excessive proliferation and migration of vascular smooth muscle cells (VSMCs) are mainly responsible for vascular occlusion diseases, such as pulmonary arterial hypertension and restenosis. Our previous study demonstrated thymoquinone (TQ) attenuated monocrotaline-induced pulmonary arterial hypertension. The aim of the present study is to systematically examine inhibitory effects of TQ on platelet-derived growth factor-BB (PDGF-BB)-induced proliferation and migration of VSMCs in vitro and neointimal formation in vivo and elucidate the potential mechanisms. Vascular smooth muscle cells were isolated from the aorta in rats. Cell viability and proliferation were measured in VSMCs using the MTT assay. Cell migration was detected by wound healing assay and Transwell assay. Alpha-smooth muscle actin (α-SMA) and Ki-67-positive cells were examined by immunofluorescence staining. Reactive oxygen species (ROS) generation and apoptosis were measured by flow cytometry and terminal deoxyribonucleotide transferase-mediated dUTP nick end labelling (TUNEL) staining, respectively. Molecules including the mitochondria-dependent apoptosis factors, matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), PTEN/AKT and mitogen-activated protein kinases (MAPKs) were determined by Western blot. Neointimal formation was induced by ligation in male Sprague Dawley rats and evaluated by HE staining. Thymoquinone inhibited PDGF-BB-induced VSMC proliferation and the increase in α-SMA and Ki-67-positive cells. Thymoquinone also induced apoptosis via mitochondria-dependent apoptosis pathway and p38MAPK. Thymoquinone blocked VSMC migration by inhibiting MMP2. Finally, TQ reversed neointimal formation induced by ligation in rats. Thus, TQ is a potential candidate for the prevention and treatment of occlusive vascular diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Movimiento Celular
/
Benzoquinonas
/
Miocitos del Músculo Liso
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Proliferación Celular
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Neointima
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Becaplermina
Límite:
Animals
Idioma:
En
Revista:
J Cell Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2019
Tipo del documento:
Article
País de afiliación:
China