Keywords
TGF-β1, Especies reactivas de oxígeno, ILK, ERK, AKT, Angiotensina II, TGF-β1, Reactive oxygen species, ILK, ERK, AKT, Angiotensin II
Integrin-linked kinase mediates the hydrogen peroxide-dependent transforming growth factor-β1 up-regulation
Abstract
El factor de crecimiento transformante β1 (TGF-β1) desempeña un papel central en procesos patológicos asociados con la acumulación de proteínas de la matriz extracelular y la fibrosis. Este estudio analiza si la regulación de TGF-β1 dependiente del peróxido de hidrógeno está mediada por la quinasa ligada a integrinas (ILK). En células mesangiales humanas, el peróxido de hidrógeno incrementó la expresión y actividad promotora de TGF-β1. Mediante inhibidores farmacológicos y silenciamiento de ILK con siRNA, se demostró la participación de la vía de señalización PI3K/ILK/AKT/ERK MAPK. Asimismo, los experimentos con angiotensina II confirmaron la relevancia fisiológica del mecanismo. Los resultados indican que los cambios en la actividad de ILK pueden mediar la sobreexpresión de TGF-β1 inducida por diferentes estímulos en condiciones fisiológicas y patológicas.
Transforming growth factor type-β1 (TGF-β1) has been recognized as a central mediator in pathological events associated with extracellular matrix protein accumulation and fibrosis. This study investigates whether hydrogen peroxide-dependent regulation of TGF-β1 is mediated by integrin-linked kinase (ILK). In human mesangial cells, hydrogen peroxide increased TGF-β1 expression and promoter activity. Using pharmacological inhibitors and ILK knockdown with small interfering RNA, the study demonstrated the involvement of the PI3K/ILK/AKT/ERK MAPK signaling pathway in hydrogen peroxide-induced TGF-β1 overexpression. Experiments using angiotensin II, a physiological stimulus of hydrogen peroxide synthesis, further confirmed the relevance of this mechanism. Overall, the results provide evidence that changes in ILK activity can mediate TGF-β1 up-regulation in response to different stimuli under pathological and physiological conditions.
Transforming growth factor type-β1 (TGF-β1) has been recognized as a central mediator in pathological events associated with extracellular matrix protein accumulation and fibrosis. This study investigates whether hydrogen peroxide-dependent regulation of TGF-β1 is mediated by integrin-linked kinase (ILK). In human mesangial cells, hydrogen peroxide increased TGF-β1 expression and promoter activity. Using pharmacological inhibitors and ILK knockdown with small interfering RNA, the study demonstrated the involvement of the PI3K/ILK/AKT/ERK MAPK signaling pathway in hydrogen peroxide-induced TGF-β1 overexpression. Experiments using angiotensin II, a physiological stimulus of hydrogen peroxide synthesis, further confirmed the relevance of this mechanism. Overall, the results provide evidence that changes in ILK activity can mediate TGF-β1 up-regulation in response to different stimuli under pathological and physiological conditions.
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