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Astragalin inhibition of oxidative stress‐induced airway epithelial fibrosis by blocking autophagy and mitochondrial dysfunction (1045.30)
Author(s) -
Cho InHee,
Gong JuHyun,
Kang YoungHee
Publication year - 2014
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.28.1_supplement.1045.30
Subject(s) - autophagy , oxidative stress , astragalin , pi3k/akt/mtor pathway , fibrosis , chemistry , reactive oxygen species , microbiology and biotechnology , autophagosome , pulmonary fibrosis , pharmacology , medicine , biology , signal transduction , apoptosis , biochemistry , kaempferol , antioxidant , quercetin
Chronic asthma is characterized by ongoing airway inflammation with involvement of reactive oxygen species (ROS) in the cellular signaling cascades, leading to subepithelial fibrosis. This study examined that 72 h‐exposure of 20 μM H 2 O 2 promoted airway fibrosis with concurrent loss of E‐cadherin and induction of collagen type 1 in airway epithelial BEAS‐2B cells, which was reversed by astragalin non‐toxic at 1‐20 μM. This study further investigated that the regulation of autophagy was responsible for inducing airway fibrosis. Growing evidence has revealed the crucial involvement of autophagy in the ROS‐associated pathogenic processes underlying pulmonary diseases. H 2 O 2 highly enhanced the induction of the autophagy‐related beclin‐1 expression within 48 h. Astragalin blocked the beclin‐1 induction and mTOR activation by H 2 O 2 , indicating that this compound may inhibit ROS‐promoted the initiation of the formation of the autophagosome in autophagy. In addition, astragalin deterred the expression induction of the mitophagy marker LC3A/B in 48 h‐H 2 O 2 ‐exposed BEAS‐2B cells. These results demonstrate that dietary astragalin can be effective in blocking ROS‐promoted bronchial epithelial fibrosis by inhibiting autophagosome initiation through mTOR activation and by ameliorating mitochondrial dysfunction. Grant Funding Source : Supported by Brain Korea 21 plus