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Life Sci. 2016 May 15;153:1-8. doi: 10.1016/j.lfs.2016.04.023. Epub 2016 Apr 19.

Diosmetin prevents TGF-β1-induced epithelial-mesenchymal transition via ROS/MAPK signaling pathways.

Author information

1
Department of Respiratory & Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
2
Department of Respiratory & Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China; Department of Respiratory & Critical Care Medicine, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai West Road, Xuzhou, Jiangsu 221000, China.
3
Department of Respiratory & Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China; Department of Respiratory & Critical Care Medicine, The Second People's Hospital of Wuhu, 263 Jiuhuashan Road, Wuhu, Anhui 241001, China.
4
Department of Respiratory & Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China. Electronic address: zeng_xiao_ning@hotmail.com.
5
Department of Respiratory & Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China. Electronic address: huangmao6114@126.com.

Abstract

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-β1 (TGF-β1)-induced EMT with underlying mechanisms in human bronchial epithelial (HBE) cells.

MAIN METHODS:

HBE cells were incubated with TGF-β1 (10ng/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-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.

SIGNIFICANCE:

Our 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.

KEYWORDS:

Diosmetin; EMT; MAPK; ROS; TGF-β1

PMID:
27101925
DOI:
10.1016/j.lfs.2016.04.023
[Indexed for MEDLINE]

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