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La activación de gp130 transduce las señales hipertróficas a través de STAT3 en los miocitos cardíacos
1Department of Medicine III, Osaka University Medical School, Suita, Japan.
Circulation
|August 26, 1998
Resumen
La vía STAT3, aguas abajo de gp130, promueve la hipertrofia de los miocitos cardíacos. Este estudio investigó el STAT3.
Área de la Ciencia:
- Biología Cardiovascular Biología Cardiovascular
- Biología celular molecular Biología celular molecular
- Transducción de señales Transducción de señales.
Sus antecedentes:
- gp130, un transductor de señales clave para las citoquinas relacionadas con la IL-6, está presente en los miocitos cardíacos.
- La activación de gp130 en los miocitos cardíacos está relacionada con la hipertrofia miocárdica.
- Existen dos vías principales aguas abajo: JAK/STAT y MAPK.
Objetivo del estudio:
- Investigar el papel crítico de la vía de Janus kinase / transductor de señal y activador de la transcripción (JAK / STAT), específicamente STAT3, en la hipertrofia de miocitos cardíacos dependientes de gp130.
- Para aclarar la participación de STAT3 en la mediación de la señalización de la hipertrofia en respuesta al factor inhibidor de la leucemia (LIF).
Principales métodos:
- Se utilizaron vectores de adenovirus para transfectar el tipo salvaje (AD / WT) o el tipo mutado (AD / DN) STAT3 cDNA en miocitos cardíacos murinos cultivados.
- Las células fueron estimuladas con el factor inhibidor de la leucemia (LIF).
- Se midió la expresión de los ARNm de c-fos y el factor natriurético auricular (FNA) y la síntesis de proteínas (incorporación de leucina [3H]); también se evaluó la actividad de MAPK.
Principales resultados:
- La activación de STAT3 aumentó significativamente la inducción de los ARNm c-fos y ANF y la síntesis de proteínas.
- Inhibición de la expresión de ARNm STAT3 atenuado c-fos inducido por LIF y ANF y síntesis de proteínas.
- No se observaron diferencias significativas en la actividad de MAPK entre los grupos, lo que sugiere un papel específico para STAT3.
Conclusiones:
- La vía de señalización STAT3-dependiente aguas abajo de gp130 juega un papel crítico en la promoción de la hipertrofia de los miocitos cardíacos.
- Esta vía es activada por el factor inhibidor de la leucemia (LIF) y contribuye a la remodelación cardíaca.
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