Astragaloside IV modulates TGF-β1-dependent epithelial-mesenchymal transition in bleomycin-induced pulmonary fibrosis.
Astragaloside IV modulates TGF-β1-dependent epithelial-mesenchymal transition in bleomycin-induced pulmonary fibrosis.
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黄芪甲苷 IV 调节博莱霉素诱导的肺纤维化中 TGF-β1 依赖性上皮间质转化
DOI：
10.1111/jcmm.13725
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发表时间：
2018-09
影响因子：
5.3
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Qian W;Cai X;Qian Q;Zhang W;Wang D
上皮-间质转化（EMT）在特发性肺纤维化（IPF）中起重要作用。黄芪甲苷（ASV）是一种来自黄芪的天然皂苷，在博莱霉素（BLM）诱导的肺纤维化中显示出抗纤维化特性。本研究旨在确定EMT是否参与ASV对BLM诱导的肺纤维化的有益作用，并阐明其潜在机制。正如预期的那样，在BLM诱导的IPF中，ASV对肺纤维化具有保护作用，并且ASV显著逆转BLM诱导的EMT。有趣的是，发现转化生长因子-β1（TGF-β1）上调，而Forkhead box O3 a（FOXO 3a）过度磷酸化且表达较少。然而，ASV处理抑制肺组织中TGF-β1的增加和FOXO 3a的活化。将TGF-β1给予肺泡上皮细胞A549以在体外诱导EMT。同时，TGF-β1激活磷脂酰肌醇3激酶/蛋白激酶B（PI 3 K/Akt）通路，诱导FOXO 3 a过度磷酸化和下调。发现FOXO 3a的过表达导致TGF-β1诱导的EMT的抑制。此外，ASV处理与TGF-β1或PI 3 K/Akt抑制剂类似，逆转了这些细胞变化并抑制了A549细胞中的EMT。总之，结果表明，ASV显著抑制TGF-β1/PI 3 K/Akt诱导的FOXO 3a过度磷酸化和下调，以逆转纤维化进展期间的EMT。
Epithelial‐mesenchymal transition (EMT) plays an important role in idiopathic pulmonary fibrosis (IPF). Astragaloside IV (ASV), a natural saponin from astragalus membranaceus, has shown anti‐fibrotic property in bleomycin (BLM)‐induced pulmonary fibrosis. The current study was undertaken to determine whether EMT was involved in the beneficial of ASV against BLM‐induced pulmonary fibrosis and to elucidate its potential mechanism. As expected, in BLM‐induced IPF, ASV exerted protective effects on pulmonary fibrosis and ASV significantly reversed BLM‐induced EMT. Intriguing, transforming growth factor‐β1 (TGF‐β1) was found to be up‐regulated, whereas Forkhead box O3a (FOXO3a) was hyperphosphorylated and less expressed. However, ASV treatment inhibited increased TGF‐β1 and activated FOXO3a in lung tissues. TGF‐β1 was administered to alveolar epithelial cells A549 to induce EMT in vitro. Meanwhile, stimulation with TGF‐β1‐activated phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway and induced FOXO3a hyperphosphorylated and down‐regulated. It was found that overexpression of FOXO3a leading to the suppression of TGF‐β1‐induced EMT. Moreover, ASV treatment, similar with the TGF‐β1 or PI3K/Akt inhibitor, reverted these cellular changes and inhibited EMT in A549 cells. Collectively, the results suggested that ASV significantly inhibited TGF‐β1/PI3K/Akt‐induced FOXO3a hyperphosphorylation and down‐regulation to reverse EMT during the progression of fibrosis.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
3.2
作者：
Wang, Li;Chi, Yang-Feng;Cai, Hui
通讯作者：
Cai, Hui
DOI：
10.1073/pnas.0800928105
发表时间：
2008-06-03
影响因子：
11.1
作者：
Sauer, Stephan;Bruno, Ludovica;Merkenschlager, Matthias
通讯作者：
Merkenschlager, Matthias
抑制 Wnt/β-连环蛋白信号传导可通过减弱 TGF-β 1 和 FGF-2 的表达来抑制博来霉素诱导的肺纤维化
影响因子：
3.6
作者：
Chen, Xiang;Shi, Chaowen;Meng, Xiannan;Zhang, Kaijia;Li, Xiaoyao;Wang, Cong;Xiang, Zou;Hu, Kebin;Han, Xiaodong
通讯作者：
Han, Xiaodong
影响因子：
168.9
作者：
King, Talmadge E., Jr.;Pardo, Annie;Selman, Moises
通讯作者：
Selman, Moises