Diosmetin prevents TGF-[beta]1-induced epithelial-mesenchymal transition via ROS/MAPK signaling pathways.
Ge, Ai; Ma, Yuan; Liu, Ya-Nan; Li, Ye-Shan; Gu, Hao; Zhang, Jia-Xiang; Wang, Qin-Xue; Zeng, Xiao-Ning; Huang, Mao
[Article]
Life Sciences.
153 Supplement C:1-8, May 15, 2016.
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Aims: Epithelial-mesenchymal transition (EMT) plays a critical role in airway repair and remodeling in many respiratory diseases such as asthma and pulmonary fibrosis. The flavone aglycone, diosmetin, possesses anti-remodeling activity in a murine model of chronic asthma, but little is known about its effects on EMT. Herein, we investigated whether diosmetin inhibits transforming growth factor-[beta]1 (TGF-[beta]1)-induced EMT with underlying mechanisms in human bronchial epithelial (HBE) cells.
Main methods: HBE cells were incubated with TGF-[beta]1 (10 ng/ml), either alone or in combination with diosmetin for indicated times. We measured reactive oxygen species (ROS) levels using FACScan and immunofluorescent assays. We assessed protein expression of NADPH oxidase 4 (NOX4), superoxide dismutase (SOD), catalase, Akt, Erk, p38, and phosphorylation levels of Akt, Erk and p38 by Western blot analysis.
Key findings: TGF-[beta]1 promoted EMT and ROS generation in HBE cells. Diosmetin significantly suppressed TGF-[beta]1-induced increases in cell migration and altered N-cadherin, E-cadherin, and [alpha]-smooth muscle actin expression. In addition, diosmetin prevented TGF-[beta]1-induced intracellular ROS generation, down-regulated NOX4, and up-regulated SOD and catalase expression. Furthermore, diosmetin remarkably inhibited TGF-[beta]1-induced phosphorylation of phosphoinositide 3-kinase (PI3K)/Akt and mitogen activated protein kinase (MAPK) pathways in HBE cells.
Significance: Our results demonstrate for the first time that diosmetin alleviates TGF-[beta]1-induced EMT by inhibiting ROS generation and inactivating PI3K/Akt and MAPK pathways. Our findings revealed a new role for diosmetin in reducing airway remodeling and fibrogenesis.
(C) 2016Elsevier, Inc.