Apigenin inhibits TGF-β1 induced fibroblast-to- myofibroblast transition in human lung fibroblast populations

Background: flavonoids are dietary plant compounds suspected to reduce the incidence of chronic diseases in several regions of the world. due to anti-allergic and anti-inflammatory activities,apigenin (4′,5,7,- trihydroxyflavone) is thought to interfere with crucial events in the pathomechanism of asthma. however,the effect of apigenin on tgf-β-induced fibroblast-to-myofibroblast transition (fmt) in human lung fibroblast populations,a key event in asthma progression,has not yet been addressed. methods: primary human bronchial fibroblasts (hbfs) propagated from ex vivo bronchial biopsies derived from patients with diagnosed asthma and human embryonic lung imr-90 fibroblasts were cultured in vitro and treated with tgf-β1 and apigenin. the myofibroblast fraction in fibroblast populations was evaluated by immunocytochemistry. expression of α-smooth muscle actin (α-sma) and tenascin c were assessed at the mrnaand protein level by real-time rt-pcr and immunoblotting,respectively. additionally,proliferation and viability tests and time lapse-monitoring ofmovement of individualhbfs and imr-90 cellswere evaluated. results: we show that apigenin attenuates tgf-β1-induced fmt in cultures of hbfs,and the magnitude of this attenuation was found to be similar to that observed in the established cell line of lung imr-90 fibroblasts. notably,fmt inhibition was observed at low (∼10 μm),non-cytotoxic and non-cytostatic apigenin concentrations and could be correlated with the inhibition of α-sma and tenascin c expression in hbfs at the mrna level. conclusions: our data are the first to demonstrate that apigenin inhibits the tgf-β1-induced expansion of hyper-contractile,α-smooth muscle actin - positive myofibroblasts within populations of hbfs derived from asthmatic patients. they also indicate the possible interference of apigenin with bronchial wall remodeling during the asthmatic process in vivo. copyright © 2013 by institute of pharmacology polish academy of sciences.