Substrate stiffening promotes VEGF-A functions via the PI3K/Akt/mTOR pathway.
Biochem Biophys Res Commun
; 586: 27-33, 2022 01 01.
Article
en En
| MEDLINE
| ID: mdl-34823219
ABSTRACT
While it is now well-established that substrate stiffness regulates vascular endothelial growth factor-A (VEGF-A) mediated signaling and functions, causal mechanisms remain poorly understood. Here, we report an underlying role for the PI3K/Akt/mTOR signaling pathway. This pathway is activated on stiffer substrates, is amplified by VEGF-A stimulation, and correlates with enhanced endothelial cell (EC) proliferation, contraction, pro-angiogenic secretion, and capillary-like tube formation. In the settings of advanced age-related macular degeneration, characterized by EC and retinal pigment epithelial (RPE)-mediated angiogenesis, these data implicate substrate stiffness as a novel causative mechanism and Akt/mTOR inhibition as a novel therapeutic pathway.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fosfatidilinositol 3-Quinasas
/
Mecanotransducción Celular
/
Células Endoteliales
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Factor A de Crecimiento Endotelial Vascular
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Proteínas Proto-Oncogénicas c-akt
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Epitelio Pigmentado de la Retina
/
Serina-Treonina Quinasas TOR
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2022
Tipo del documento:
Article
País de afiliación:
India