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Inhibición farmacológica de la vía PI3K/AKT/mTOR en los sinoviocitos de la artritis reumatoide: una revisión
Tatiana Bobkova1,2, Artem Bobkov3, Yang Li1,4
1Department of Rheumatology and Immunology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Pharmaceuticals (Basel, Switzerland)
|August 28, 2025
Resumen
La orientación de la vía PI3K/ AKT/ mTOR reduce significativamente la proliferación de sinoviocitos similares a los fibroblastos y la inflamación en la artritis reumatoide. Esta vía es un objetivo terapéutico validado, con p-AKT y p-mTOR sirviendo como marcadores clave de respuesta.
Área de la Ciencia:
- Biología molecular
- Inmunología
- Farmacología
Sus antecedentes:
- La activación constitutiva de la vía PI3K / AKT / mTOR impulsa el comportamiento agresivo de los sinoviocitos similares a los fibroblastos (FLS) en la artritis reumatoide (AR).
- Falta una síntesis cuantitativa de los datos in vitro sobre la inhibición de la vía PI3K/AKT/mTOR en la AR.
Objetivo del estudio:
- Revisar sistemáticamente y metaanalizar los efectos de los inhibidores de la vía PI3K/AKT/mTOR en la proliferación, la apoptosis, la migración, la secreción de citoquinas y las moléculas de señalización clave.
- Evaluar la heterogeneidad e identificar los moderadores de los efectos del tratamiento, incluidos el tipo de estímulo, la fuente celular y la clase de inhibidor.
Principales métodos:
- Búsqueda sistemática de la literatura de PubMed, Europe PMC y la Biblioteca Cochrane hasta mayo de 2025.
- Extracción de datos y evaluación de la calidad por dos revisores independientes.
- Metaanálisis de efectos aleatorios de las diferencias medias estandarizadas (Hedges g) utilizando el modelo de Sidik-Jonkman con intervalos de confianza de Hartung-Knapp.
Principales resultados:
- La inhibición de PI3K/ AKT/ mTOR redujo notablemente la proliferación de la EPL-AR (g = -5.1), la secreción de IL-6 (g = -11.1) e IL-8 (g = -6.5), al tiempo que aumentaba la apoptosis (g = +2.7).
- La mayoría de los resultados mostraron efectos grandes (gadgadgadgadg ≥ 0,8) con una heterogeneidad baja a moderada (I2 ≤ 35%).
- Los niveles de AKT fosforilado (p-AKT) y mTOR fosforilado (p-mTOR) reflejaron de manera fiable la inhibición de la vía y los cambios funcionales.
Conclusiones:
- El bloqueo dirigido de la vía PI3K/AKT/mTOR suprime efectivamente el fenotipo agresivo e inflamatorio de las ERA-FLS.
- El eje PI3K/AKT/mTOR es un objetivo terapéutico validado en la AR.
- p-AKT y p-mTOR son marcadores farmacodinámicos fiables para evaluar la respuesta al tratamiento, apoyando estrategias terapéuticas personalizadas.
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