FOXM1 c.1205 C > A mutation is associated with unilateral Moyamoya disease and inhibits angiogenesis in human brain endothelial cells.
Hum Genet
; 143(8): 939-953, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38969938
ABSTRACT
Unilateral moyamoya disease (MMD) represents a distinct subtype characterised by occlusive changes in the circle of Willis and abnormal vascular network formation. However, the aetiology and pathogenesis of unilateral MMD remain unclear. In this study, genetic screening of a family with unilateral MMD using whole-genome sequencing helped identify the c.1205 C > A variant of FOXM1, which encodes the transcription factor FOXM1 and plays a crucial role in angiogenesis and cell proliferation, as a susceptibility gene mutation. We demonstrated that this mutation significantly attenuated the proangiogenic effects of FOXM1 in human brain endothelial cells, leading to reduced proliferation, migration, and tube formation. Furthermore, FOXM1 c.1205 C > A results in increased apoptosis of human brain endothelial cells, mediated by the downregulation of the transcription of the apoptosis-inhibiting protein BCL2. These results suggest a potential role for the FOXM1 c.1205 C > A mutation in the pathogenesis of unilateral MMD and may contribute to the understanding and treatment of this condition.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
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Células Endoteliales
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Proliferación Celular
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Proteína Forkhead Box M1
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Angiogénesis
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Enfermedad de Moyamoya
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Mutación
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Hum Genet
Año:
2024
Tipo del documento:
Article
País de afiliación:
China