TRPV4 channels mediate cyclic strain-induced endothelial cell reorientation through integrin-to-integrin signaling.
Circ Res
; 104(9): 1123-30, 2009 May 08.
Article
en En
| MEDLINE
| ID: mdl-19359599
ABSTRACT
Cyclic mechanical strain produced by pulsatile blood flow regulates the orientation of endothelial cells lining blood vessels and influences critical processes such as angiogenesis. Mechanical stimulation of stretch-activated calcium channels is known to mediate this reorientation response; however, the molecular basis remains unknown. Here, we show that cyclically stretching capillary endothelial cells adherent to flexible extracellular matrix substrates activates mechanosensitive TRPV4 (transient receptor potential vanilloid 4) ion channels that, in turn, stimulate phosphatidylinositol 3-kinase-dependent activation and binding of additional beta1 integrin receptors, which promotes cytoskeletal remodeling and cell reorientation. Inhibition of integrin activation using blocking antibodies and knock down of TRPV4 channels using specific small interfering RNA suppress strain-induced capillary cell reorientation. Thus, mechanical forces that physically deform extracellular matrix may guide capillary cell reorientation through a strain-dependent "integrin-to-integrin" signaling mechanism mediated by force-induced activation of mechanically gated TRPV4 ion channels on the cell surface.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polaridad Celular
/
Integrina beta1
/
Mecanotransducción Celular
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Células Endoteliales
/
Canales Catiónicos TRPV
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Circ Res
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos