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Las metaloproteinasas de matriz regulan la neovascularización actuando como fibrinolisinas pericelulares
1Department of Internal Medicine and University of Michigan Comprehensive Cancer Center, Ann Arbor 48109, USA.
Cell
|November 14, 1998
Resumen
Las células endoteliales usan metaloproteinasas matriciales (MMP), no activadores de plasminógeno, para romper las barreras de fibrina durante la formación de nuevos vasos sanguíneos (angiogénesis). Los MMPs atados a la membrana son clave para este proceso.
Área de la Ciencia:
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
- Fisiología Fisiología Fisiología.
Sus antecedentes:
- La angiogénesis implica la invasión de las células endoteliales a través de matrices de fibrina.
- Los mecanismos proteolíticos que impulsan esta invasión no estaban previamente definidos.
- El papel del activador de plasminógeno (AP) -sistema de plasminógeno en este proceso no estaba claro.
Objetivo del estudio:
- Para dilucidar los mecanismos proteolíticos utilizados por las células endoteliales para penetrar las barreras de fibrina durante la angiogénesis.
- Determinar el papel del sistema PA-plasminógeno frente a las metaloproteinasas matriciales (MMP) en este proceso.
Principales métodos:
- Se utilizaron tejidos de ratón con deficiencia de PA y plasminógeno.
- Neovascularización evaluada de los geles de fibrina in vitro e in vivo.
- Transfección genética empleada de células endoteliales con metaloproteinasas de matriz, incluida la MMP de tipo 1 de membrana (MT1-MMP).
Principales resultados:
- La neovascularización se produjo efectivamente en tejidos con deficiencia de PA o plasminógeno, lo que indica que estos sistemas no son necesarios.
- Las MMP derivadas de las células endoteliales son esenciales para la penetración de la barrera de la fibrina durante la angiogénesis.
- La transfección con MT1-MMP ligado a la membrana restauró la invasión en células previamente incompetentes.
- Un mutante MT1-MMP eliminado de la transmembrana, pero activo, no pudo restaurar la invasión, lo que pone de relieve la importancia de la localización de la membrana.
Conclusiones:
- Se identificó una nueva vía fibrinolítica independiente de la PA, crucial para la angiogénesis.
- Se demostró que los MMPs atados a la membrana, específicamente MT1-MMP, actúan como fibrinolisinas pericelulares.
- Los MMP establecidos como reguladores clave de la invasión de las células endoteliales a través de la fibrina durante la neovascularización.
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