Emodin ameliorates bleomycin-induced pulmonary fibrosis in rats by suppressing epithelial-mesenchymal transition and fibroblast activation.
Emodin ameliorates bleomycin-induced pulmonary fibrosis in rats by suppressing epithelial-mesenchymal transition and fibroblast activation.
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大黄素通过抑制上皮间质转化和成纤维细胞活化改善博莱霉素诱导的大鼠肺纤维化
DOI：
10.1038/srep35696
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发表时间：
2016-10-24
影响因子：
4.6
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Guan R;Wang X;Zhao X;Song N;Zhu J;Wang J;Wang J;Xia C;Chen Y;Zhu D;Shen L
TGF-β1的异常活化是肺纤维化中经常遇到的，并促进上皮-间充质转化（EMT）和成纤维细胞活化。本研究探讨大黄素是否通过抑制TGF-β1诱导的EMT和成纤维细胞活化介导其在博莱霉素（BLM）诱导的大鼠肺纤维化中的作用。我们发现大黄素可诱导TGF-β1刺激的人胚肺成纤维细胞（HELFs）凋亡，并抑制细胞增殖、迁移和分化。大黄素抑制TGF-β1诱导的肺泡上皮A549细胞EMT，并呈剂量和时间依赖性。大黄素还抑制TGF-β1诱导的Smad 2、Smad 3和Erk 1/2的激活，提示Smad 2/3和Erk 1/2的失活介导了大黄素对TGF-β1诱导的EMT的影响。此外，我们提供的体内证据表明，大黄素明显减轻BLM诱导的肺纤维化和改善肺功能，抑制TGF-β1信号传导，随后抑制EMT，成纤维细胞活化和细胞外基质（ECM）沉积。总之，我们的数据表明，大黄素介导其作用主要是通过抑制EMT和成纤维细胞活化，因此具有治疗肺纤维化的潜力。
Aberrant activation of TGF-β1 is frequently encountered and promotes epithelial-mesenchymal transition (EMT) and fibroblast activation in pulmonary fibrosis. The present study investigated whether emodin mediates its effect via suppressing TGF-β1-induced EMT and fibroblast activation in bleomycin (BLM)-induced pulmonary fibrosis in rats. Here, we found that emodin induced apoptosis and inhibited cellular proliferation, migration and differentiation in TGF-β1-stimulated human embryonic lung fibroblasts (HELFs). Emodin suppressed TGF-β1-induced EMT in a dose- and time-dependent manner in alveolar epithelial A549 cells. Emodin also inhibited TGF-β1-induced Smad2, Smad3 and Erk1/2 activation, suggesting that Smad2/3 and Erk1/2 inactivation mediated the emodin-induced effects on TGF-β1-induced EMT. Additionally, we provided in vivo evidence suggesting that emodin apparently alleviated BLM-induced pulmonary fibrosis and improved pulmonary function by inhibiting TGF-β1 signaling and subsequently repressing EMT, fibroblast activation and extracellular matrix (ECM) deposition. Taken together, our data suggest that emodin mediates its effects mainly via inhibition of EMT and fibroblast activation and thus has a potential for the treatment of pulmonary fibrosis.
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甘草酸减轻博莱霉素诱导的大鼠肺纤维化
影响因子：
5.6
作者：
Gao L;Tang H;He H;Liu J;Mao J;Ji H;Lin H;Wu T
通讯作者：
Wu T
DOI：
10.1165/ajrcmb/5.2.155
发表时间：
1991-08-01
影响因子：
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作者：
KHALIL, N;OCONNOR, RN;GREENBERG, AH
通讯作者：
GREENBERG, AH
影响因子：
2.9
作者：
Lorena, D;Uchio, K;Desmoulière, A
通讯作者：
Desmoulière, A
影响因子：
9
作者：
Chen, Y-L;Zhang, X.;Bai, J.;Gai, L.;Ye, X-L;Zhang, L.;Xu, Q.;Zhang, Y-X;Xu, L.;Li, H-P;Ding, X.
通讯作者：
Ding, X.
DOI：
10.1164/rccm.2009-040gl
发表时间：
2011-03-15
影响因子：
24.7
作者：
Raghu, Ganesh;Collard, Harold R.;Schuenemann, Holger J.
通讯作者：
Schuenemann, Holger J.