Emodin inhibiting neutrophil elastase-induced epithelial-mesenchymal transition through Notch1 signalling in alveolar epithelial cells.
Emodin inhibiting neutrophil elastase-induced epithelial-mesenchymal transition through Notch1 signalling in alveolar epithelial cells.
复制标题
大黄素通过肺泡上皮细胞中Notch1信号传导抑制中性粒细胞弹性蛋白酶诱导的上皮间质转化
DOI：
10.1111/jcmm.15827
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发表时间：
2020-10
影响因子：
5.3
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Zhou L;Gao R;Hong H;Li X;Yang J;Shen W;Wang Z;Yang J
据报道，肺泡II型上皮细胞向成纤维细胞的转变导致和/或加重肺纤维化（PF），其特征在于成纤维细胞增殖、ECM（细胞外基质）的产生和积累增强、肺泡壁损伤和功能性毛细血管单位损失。已有报道中药大黄素通过Notch信号通路抑制TGF-β诱导的肺泡上皮细胞上皮间质转化（EMT）。在本研究中，中性粒细胞弹性蛋白酶（NE，也称为ELA 2）处理促进了RLE-6 TN细胞和A549细胞中的EMT、Notch 1切割（NICD/Notch 1比率增加）和NICD核转位。NE治疗在这些事件中的促进作用被Notch 1敲低显著逆转。中药大黄素处理可显著抑制NE酶活性，抑制RLE-6 TN和A549细胞EMT、Notch 1裂解和NICD核转位，而NE处理可显著逆转大黄素的作用。此外，在RLE-6 TN中，NE对EMT、Notch 1切割和NICD核转位的作用被大黄素处理显著减弱，并且大黄素和中性粒细胞弹性蛋白酶抑制剂Sivelestat或notch信号通路抑制剂DAPT的组合更能减弱。总之，我们揭示了NE诱导的Notch 1切割参与大黄素抑制NE引起的RLE-6 TN细胞和A549细胞中的EMT的功能。大黄素抑制EMT的新机制为大黄素在PF治疗中的应用提供了可能。
The transition of alveolar type II epithelial cells into fibroblasts has been reported to cause and/or aggravate pulmonary fibrosis (PF), which is characterized by fibroblast proliferation, an enhanced production and accumulation of ECM (extracellular matrix), alveolar wall damage and functional capillary unit loss. Traditional Chinese medicine Emodin has been reported to inhibit TGF‐β‐induced epithelial‐mesenchymal transition (EMT) in alveolar epithelial cells through Notch signalling. In the present study, neutrophil elastase (NE, also known as ELA2) treatment promoted EMT, Notch1 cleavage (NICD/Notch1 ratio increase) and NICD nuclear translocation in RLE‐6TN cells and A549 cells. The promotive roles of NE treatment in these events were significantly reversed by Notch1 knockdown. Traditional Chinese medicine Emodin treatment remarkably inhibited the enzyme activity of NE, suppressed EMT, Notch1 cleavage and NICD nuclear translocation within RLE‐6TN and A549 cells, while NE treatment significantly reversed the effects of Emodin. Moreover, in RLE‐6TN, the effects of NE on EMT, Notch1 cleavage and NICD nuclear translocation were remarkably attenuated by Emodin treatment and more attenuated by the combination of Emodin and neutrophil elastase inhibitor Sivelestat or notch signal pathway inhibitor DAPT. In conclusion, we revealed the involvement of NE‐induced Notch1 cleavage in the functions of Emodin suppressing NE‐caused EMT in RLE‐6TN cells and A549 cells. This novel mechanism of Emodin inhibiting EMT might extend the application of Emodin in PF treatment.
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影响因子：
10.5
作者：
Timmerman, LA;Grego-Bessa, J;de la Pompa, JL
通讯作者：
de la Pompa, JL
影响因子：
4
作者：
Kim, Jeongyub;Lee, Jong-Seon;Park, Myung-Jin
通讯作者：
Park, Myung-Jin
影响因子：
3.9
作者：
STEIN, RL
通讯作者：
STEIN, RL
影响因子：
3.9
作者：
Mayer C;Darb-Esfahani S;Meyer AS;Hübner K;Rom J;Sohn C;Braicu I;Sehouli J;Hänsch GM;Gaida MM
通讯作者：
Gaida MM
影响因子：
6
作者：
Liu, Tianju;Hu, Biao;Phan, Sem H.
通讯作者：
Phan, Sem H.