کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2550550 | 1560575 | 2016 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Diosmetin prevents TGF-β1-induced epithelial-mesenchymal transition via ROS/MAPK signaling pathways Diosmetin prevents TGF-β1-induced epithelial-mesenchymal transition via ROS/MAPK signaling pathways](/preview/png/2550550.png)
AimsEpithelial-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-β1 (TGF-β1)-induced EMT with underlying mechanisms in human bronchial epithelial (HBE) cells.Main methodsHBE cells were incubated with TGF-β1 (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 findingsTGF-β1 promoted EMT and ROS generation in HBE cells. Diosmetin significantly suppressed TGF-β1-induced increases in cell migration and altered N-cadherin, E-cadherin, and α-smooth muscle actin expression. In addition, diosmetin prevented TGF-β1-induced intracellular ROS generation, down-regulated NOX4, and up-regulated SOD and catalase expression. Furthermore, diosmetin remarkably inhibited TGF-β1-induced phosphorylation of phosphoinositide 3-kinase (PI3K)/Akt and mitogen activated protein kinase (MAPK) pathways in HBE cells.SignificanceOur results demonstrate for the first time that diosmetin alleviates TGF-β1-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.
Journal: Life Sciences - Volume 153, 15 May 2016, Pages 1–8