SB203580-A Potent p38 MAPK Inhibitor Reduces the Profibrotic Bronchial Fibroblasts Transition Associated with Asthma.
Int J Mol Sci
; 22(23)2021 Nov 26.
Article
en En
| MEDLINE
| ID: mdl-34884593
ABSTRACT
Subepithelial fibrosis is a component of the remodeling observed in the bronchial wall of patients diagnosed with asthma. In this process, human bronchial fibroblasts (HBFs) drive the fibroblast-to-myofibroblast transition (FMT) in response to transforming growth factor-ß1 (TGF-ß1), which activates the canonical Smad-dependent signaling. However, the pleiotropic properties of TGF-ß1 also promote the activation of non-canonical signaling pathways which can affect the FMT. In this study we investigated the effect of p38 mitogen-activated protein kinase (MAPK) inhibition by SB203580 on the FMT potential of HBFs derived from asthmatic patients using immunocytofluorescence, real-time PCR and Western blotting methods. Our results demonstrate for the first time the strong effect of p38 MAPK inhibition on the TGF-ß1-induced FMT potential throughout the strong attenuation of myofibroblast-related markers α-smooth muscle actin (α-SMA), collagen I, fibronectin and connexin 43 in HBFs. We suggest the pleiotropic mechanism of SB203580 on FMT impairment in HBF populations by the diminishing of TGF-ß/Smad signaling activation and disturbances in the actin cytoskeleton architecture along with the maturation of focal adhesion sites. These observations justify future research on the role of p38 kinase in FMT efficiency and bronchial wall remodeling in asthma.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Piridinas
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Asma
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Bronquios
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Diferenciación Celular
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Proteínas Quinasas p38 Activadas por Mitógenos
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Inhibidores Enzimáticos
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Fibroblastos
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Imidazoles
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Int J Mol Sci
Año:
2021
Tipo del documento:
Article
País de afiliación:
Polonia