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Modified Yeast-Two-Hybrid System to Identify Proteins Interacting with the Growth Factor Progranulin
Published on: January 17, 2012
El factor de crecimiento progranulina se une a los receptores TNF y es terapéutico contra la artritis inflamatoria en
Wei Tang1, Yi Lu, Qing-Yun Tian
1Department of Orthopaedic Surgery, New York University School of Medicine and NYU Hospital for Joint Diseases, New York, NY 10003, USA.
Science (New York, N.Y.)
|March 12, 2011
Resumen
La progranulina (PGRN) se une a los receptores del factor de necrosis tumoral (TNFR), actuando como un antagonista de la señalización TNFα. Este descubrimiento ofrece nuevas vías terapéuticas para enfermedades inflamatorias como la artritis.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- La progranulina (PGRN) es un factor de crecimiento involucrado en el desarrollo, la reparación y la inflamación.
- Los receptores específicos para el PGRN han permanecido sin identificar.
- La señalización del factor de necrosis tumoral alfa (TNFα) es una vía clave en las enfermedades inflamatorias.
Objetivo del estudio:
- Para identificar los receptores para la progranulina (PGRN).
- Para investigar el papel de la PGRN en la artritis inflamatoria.
- Explorar la PGRN y sus derivados como terapias potenciales para enfermedades mediadas por el TNFα.
Principales métodos:
- Pruebas bioquímicas para evaluar la unión de la PGRN a los receptores del factor de necrosis tumoral (TNFR).
- Estudios con ratones con deficiencia de PGRN para evaluar la susceptibilidad a la artritis inducida por el colágeno.
- Administración de PGRN y una proteína derivada de PGRN (Atsttrin) en modelos de ratón de artritis inflamatoria.
- Análisis de las vías de señalización intracelular activadas por TNFα.
Principales resultados:
- La progranulina (PGRN) se une directamente a los receptores del factor de necrosis tumoral (TNFR), interrumpiendo la interacción TNFα-TNFR.
- Los ratones con deficiencia de PGRN mostraron una mayor susceptibilidad a la artritis inducida por el colágeno.
- La administración de PGRN y Atsttrin mejoró la inflamación en modelos de artritis.
- PGRN y Atsttrin inhibían la señalización intracelular activada por el TNFα.
Conclusiones:
- La progranulina (PGRN) funciona como un ligando para el TNFR y un antagonista de la señalización TNFα.
- El PGRN juega un papel crítico en la patogénesis de la artritis inflamatoria en ratones.
- PGRN y sus variantes de ingeniería representan candidatos terapéuticos prometedores para afecciones inflamatorias relacionadas con el TNFα, incluida la artritis reumatoide.
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