Abstract
Subepithelial fibrosis (SF) is a key phenomenon responsible for irreversible obturation of bronchi and bronchial remodelling during asthma. Many cellular (proliferation, apoptosis, myofibroblastic transition (FMT) of fibroblasts) and extracellular factors (enhanced secretion of pro-inflammatory cytokines, growth factors, extracellular matrix (ECM) proteins) are involved in the progression of SF. Since asthma therapies have a negligible effect on SF, searching for compounds capable to reduce or reverse this process is particularly important.
Based on the suggested anti-inflammatory and anti-fibrotic properties of chalcones, we have chosen isoliquiritigenin (ISL) and flavokawain A (FKA) to check their impact on the asthma-related FMT.
Bronchial fibroblasts derived from asthmatics were treated by ISL and FKA (in non-cytotoxic concentrations) and co-treated with TGF-β1 (5 ng/ml) for 24 h (PCR) and 5 days (immunofluorescence, immunoblots, In-Cell ELISA).
We observed reduction of the TGF-β1-induced myofibroblasts formation after ISL and FKA treatment. This correlated with decrease in expression of myofibroblast markers: ACTA2, TAGLN, PAI-1. Though ISL and FKA had minor effect on ECM gene expression (COL3, FN, TNC), they significantly increased the expression ratio of MMP9/TIMP3, which was reduced after the TGF-β1 treatment. Additionally, ISL and FKA reduced the CCN2 expression.
In fine, we observed pleiotropic inhibitory effects of tested chalcones on the FMT efficiency through influence on cellular and extracellular FMT-related factors regulated by Smad- and non-Smad-dependent pathways.
Financing: Etiuda 2019/32/T/NZ3/00405; N19/MNS/000038
Footnotes
Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA3688.
This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2021