RT Journal Article
SR Electronic
T1 Chalcones: isoliquiritigenin and flavokawain A reduce asthma-related fibroblast to myofibroblast transition, intensified by TGF-ß1
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA3688
DO 10.1183/13993003.congress-2021.PA3688
VO 58
IS suppl 65
A1 Dawid Wnuk
A1 Alicja Ślusarczyk
A1 Milena Paw
A1 Justyna Drukała
A1 Marta Michalik
YR 2021
UL http://erj.ersjournals.com/content/58/suppl_65/PA3688.abstract
AB 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/000038FootnotesCite 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).