Apigenin inhibits TGF-β1 induced fibroblast-to-myofibroblast transition in human lung fibroblast populations.
Journal Title: Pharmacological Reports - Year 2013, Vol 65, Issue 1
Abstract
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 mRNA and protein level by real-time RT-PCR and immunoblotting, respectively. Additionally, proliferation and viability tests and time lapse-monitoring of movement of individual HBFs and IMR-90 cells were 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.
Authors and Affiliations
Katarzyna Wójcik, Marta Skoda, Paulina Koczurkiewicz, Marek Sanak, Jarosław Czyż
Keywords
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