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La activación de la proteasa de las células endoteliales activa el receptor 1 por la vía de la proteína C
Matthias Riewald1, Ramona J Petrovan, Aaron Donner
1Department of Immunology, C204, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science (New York, N.Y.)
|June 8, 2002
Resumen
La vía de la proteína C (PC) protege contra la sepsis. El PC activado (APC) utiliza EPCR para señalar a través de PAR1, induciendo genes protectores como MCP-1, cruciales para la defensa de la sepsis.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Inmunología Inmunología.
Sus antecedentes:
- La sepsis implica la coagulación y la inflamación dañinas.
- La vía de la proteína C (PC) ofrece protección contra la sepsis.
- La proteína C activada (APC) interactúa con las células endoteliales.
Objetivo del estudio:
- Para investigar el mecanismo de los efectos protectores de APC en la sepsis.
- Para identificar el receptor específico y la vía de señalización involucrada en las acciones protectoras de APC.
- Para determinar si la señalización PAR1 media la expresión génica protectora inducida por APC.
Principales métodos:
- Perfiles genéticos para analizar cambios en la expresión génica inducidos por APC.
- Investigando el papel del receptor de PC de las células endoteliales (EPCR) como un coreceptor.
- Examinando la escisión del receptor activado por proteasa 1 (PAR1) por APC.
- Comparando la señalización a través de PAR1 versus PAR2.
Principales resultados:
- APC utiliza EPCR como un coreceptor para la escisión de PAR1 en las células endoteliales.
- La señalización PAR1 explica completamente la inducción de todos los genes protectores de APC.
- La proteína monocítica quimioatractante-1 (MCP-1), un gen inmunomodulador, fue inducida selectivamente por la activación de PAR1.
- La activación de PAR2 no indujo el MCP-1.
Conclusiones:
- El receptor de trombina prototipo, PAR1, es el objetivo de la señalización APC dependiente del EPCR.
- Esta cascada de receptores juega un papel importante en la protección contra la sepsis.
- Dirigirse a la vía EPCR-PAR1 podría ofrecer estrategias terapéuticas para la sepsis.
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