Inhibition of p38 MAPK by SB203580 strongly attenuated the TGF-β1-induced fibroblast-to-myofibroblast transition in human bronchial fibroblasts from asthmatic patients.
SB203580 reduces profibrotic transition in human bronchial fibroblasts, suggesting a potential role for p38 MAPK inhibition in preventing bronchial wall remodeling in asthma.
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-β1 (TGF-β1), which activates the canonical Smad-dependent signaling. However, the pleiotropic properties of TGF-β1 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-β1-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-β/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.
Paw et al. (2021) studied Asthma. SB203580 (p38 MAPK inhibitor) was evaluated on Fibroblast-to-myofibroblast transition (FMT) potential and myofibroblast-related markers. Inhibition of p38 MAPK by SB203580 strongly attenuated the TGF-β1-induced fibroblast-to-myofibroblast transition in human bronchial fibroblasts from asthmatic patients.