Orientin attenuates pulmonary fibrosis via TGF-β1/suppressor of mother against decapentaplegic 3 (Smad3) pathway.

La orientina reduce la fibrosis pulmonar mediante la vía de señalización TGF-β1/Smad3.

• Yijin Liu Department of Pharmacy, Liaoning University of Traditional Chinese Medicine Xinglin College, Shenyang, Liaoning Province, China. https://orcid.org/0009-0000-9374-5973
• Yao Lu Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, China. https://orcid.org/0009-0007-2749-1419

DOI: https://doi.org/10.54817/IC.v67n2a07

Palabras clave: Orientin, Fibrosis pulmonar, Fibroblastos, Vía de TGF-β1/Smad3

Resumen

La orientina, un flavonoide natural presente en una variedad de plantas medicinales, reduce el daño pulmonar gracias a sus efectos antiinflamatorios y antioxidantes. Sin embargo, no se han reportado estudios sobre su efecto en la fibrosis pulmonar (PF). Las células Human Fetal Lung 1 (HFL1) se estimularon con el factor de crecimiento transformante β1 (TGF-β1) y se administró una dosis única de bleomicina por vía intratraqueal para establecer un modelo de PF en ratones. La intervención se realizó con orientina, el agonista SRI-011381 de la vía supresora de madre contra el decapentapléjico 3, y el in- hibidor SB431542. La proliferación y migración de células HFL1 se evaluaron mediante el Kit-8 (CCK-8) para el conteo de células, la tinción de Edu (para evaluar la actividad proliferativa) y mediante el ensayo de cicatrización de heridas. Las fibras en las células HFL1 se detectaron mediante tinción con Sirius Red. La inflamación y la fibrosis del tejido pulmonar se evaluaron mediante tinción patológica y ensayo inmunoenzimático ligado a anticuerpos (ELISA). Los niveles de expresión proteica de PF y de la vía TGF-β1/Smad3 se analizaron mediante Western blot. La orientina reduce significativamente los niveles de las proteínas TGF-β1, p-Smad3, actina alfa del músculo liso (α-SMA), colágeno I y metalopeptidasa de la matriz (MMP)-2. Además, el tratamiento con orientina disminuyó significativamente las células Edu positivas, la proliferación y la migración de las células HFL1, así como la formación de fibras de colágeno teñidas de rojo. El tra- tamiento con orientina redujo el deterioro de la cavidad alveolar, el infiltrado de células inflamatorias y la hiperplasia de fibras colágenas en el tejido pulmonar de los ratones, y disminuyó significativamente el contenido de Hydroxyproline (HYP) y de los factores inflamatorios (TNF-α e IL -6) en el lavado alveolar. Sin embargo, SRI-011381 atenuó el efecto de la intervención con orientina, con un aumento significativo de los niveles de inflamación y fibrosis; el SB431542 lo acentuó. La orientina inhibe la vía de señalización TGF-β1/Smad3, la transición de fibroblastos a miofibroblastos (FMT) y la producción de matriz extracelular (ECM), y alivia el daño inflamatorio y fibroso.

Citas

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