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Kaempferol suppresses lung airway fibrosis through modulating TGF‐β‐PAR‐1 activation in human bronchial epithelial cells and ovalbumin‐challenged mice
Author(s) -
Gong JuHyun,
Kang YoungHee
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.861.20
Subject(s) - ovalbumin , fibrosis , lung , pulmonary fibrosis , airway , secretion , chemistry , mucus , kaempferol , immunology , pathology , cancer research , medicine , biology , endocrinology , immune system , quercetin , ecology , biochemistry , surgery , antioxidant
Chronic airway remodeling is characterized by structural changes within the airway wall, including smooth muscle hypertrophy, sub‐mucosal fibrosis and epithelial shedding. Epithelial to mesenchymal transition (EMT) is a fundamental mechanism of organ fibrosis, which can be induced by TGF‐β1. Protease‐activated receptor (PAR) has been known to contribute to the pathogenesis of various pulmonary diseases. However, little is known about the localization of PAR‐1 in lung airway and relationship between PAR‐1 and EMT. In vitro study, we investigated whether kaempferol inhibited TGF‐β1‐induced bronchial epithelial EMT for 72 h. TGF‐β1 resulted in a striking loss of epithelial morphology by displaying fibroblast appearance. Kaempferol at ≤20 μM significantly inhibited TGF‐β1‐induced collagen secretion and α‐SMA induction through disturbing PAR1 activation dampened by SCH‐79797. In vivo study explored demoting effects of 10–20 mg/kg kaempferol on airway constriction responses in BALB/c mice sensitized with OVA. Kaempferol suppressed collagen deposition, smooth muscle cell excrescency and mucus secretion observed in the lung of OVA‐challenged mice. These results demonstrate that dietary kaempferol alleviated fibrotic airway remodeling via bronchial epithelial EMT by modulating PAR1 activation. Therefore, kaempferol may be a potential therapeutic agent targeting asthmatic airway constriction.