Andrographolide attenuates epithelial-mesenchymal transition induced by TGF-β1 in alveolar epithelial cells

被引：35
作者：
Li, Jingpei [1 ,2 ]
Liu, Jun [1 ,2 ]
Yue, Weifeng [2 ]
Xu, Ke [1 ,2 ]
Cai, Weipeng [1 ,2 ]
Cui, Fei [1 ,2 ]
Li, Zhuoyi [1 ,2 ]
Wang, Wei [1 ,2 ]
He, Jianxing [1 ,2 ]
机构：
[1] Guangzhou Med Univ, Dept Thorac Surg, Affiliated Hosp 1, Guangzhou 510120, Peoples R China
[2] Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Resp Dis, Guangzhou Inst Resp Hlth, Guangzhou, Peoples R China
来源：
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE | 2020年 / 24卷 / 18期
基金：
中国国家自然科学基金;
关键词：
alveolar epithelial cells; andrographolide; EMT; oxidative stress; Sirt1/FOXO3; signalling; TGF-beta; 1; IDIOPATHIC PULMONARY-FIBROSIS; TGF-BETA; INHIBITION; RESPONSES; GROWTH; INJURY; PLAYS; FOXO3; MICE;
D O I：
10.1111/jcmm.15665
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Andrographolide (Andro), a component from Chinese medicinal herb Andrographis paniculata, could alleviate pulmonary fibrosis in rodents. Yet, whether and how Andro mitigates epithelial-mesenchymal transition (EMT) induced by TGF-beta 1 remain unknown. This study aimed to explore the effect of Andro on TGF-beta 1-induced EMT in human alveolar epithelial cells (AECs) and the mechanisms involved. We illustrated that Andro inhibited TGF-beta 1-induced EMT and EMT-related transcription factors in alveolar epithelial A549 cells. Andro also reduced TGF-beta 1-induced cell migration and synthesis of pro-fibrotic factors (ie CCN-2, TGF-beta 1), matrix metalloproteinases (ie MMP-2, MMP-9) and extracellular matrix (ECM) components (ie collagen 1), implying the inhibiting effect of Andro on TGF-beta 1-induced EMT-like cell behaviours. Mechanistically, Andro treatment not only repressed TGF-beta 1-induced Smad2/3 phosphorylation and Smad4 nuclear translocation, but also suppressed TGF-beta 1-induced Erk1/2 phosphorylation and nuclear translocation in A549 cells. And treatment with ALK5 inhibitor (SB431542) or Erk1/2 inhibitors (SCH772984 and PD98059) remarkably reduced EMT evoked by TGF-beta 1. In addition, Andro also reduced TGF-beta 1-induced intracellular ROS generation and NOX4 expression, and elevated antioxidant superoxide dismutase 2 (SOD2) expression, demonstrating the inhibiting effect of Andro on TGF-beta 1-induced oxidative stress, which is closely linked to EMT. Furthermore, Andro remarkably attenuated TGF-beta 1-induced down-regulation of sirtuin1 (Sirt1) and forkhead box O3 (FOXO3), implying that Andro protects AECs from EMT partially by activating Sirt1/FOXO3-mediated anti-oxidative stress pathway. In conclusion, Andro represses TGF-beta 1-induced EMT in AECs by suppressing Smad2/3 and Erk1/2 signalling pathways and is also closely linked to the activation of sirt1/FOXO3-mediated anti-oxidative stress pathway.
引用
收藏
页码：10501 / 10511
页数：11
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