Tanshinone IIA attenuates silica-induced pulmonary fibrosis via Nrf2-mediated inhibition of EMT and TGF-β1/Smad signaling
Tanshinone IIA attenuates silica-induced pulmonary fibrosis via Nrf2-mediated inhibition of EMT and TGF-β1/Smad signaling
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DOI：
10.1016/j.cbi.2020.109024
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发表时间：
2020-03-01
影响因子：
5.1
通讯作者：
Wang, Wei
中科院分区：
文献类型：
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作者：
Feng, Feifei;Cheng, Peng;Wang, Wei
矽肺病是由吸入二氧化硅（SiO2）引起的职业性肺纤维化，目前尚无有效的药物治疗此病。丹参酮IIA （Tan IIA）是一种天然产物，对多种疾病具有抗氧化和抗纤维化的作用。本研究的目的是研究Tan IIA对二氧化硅诱导的肺纤维化的保护作用，并探讨其潜在机制。我们通过组织和免疫组织化学分析发现，在体内用Tan IIA治疗可显著减轻矽肺模型大鼠的肺纤维化。此外，以western blot和免疫荧光分析为主的体外机制研究显示，Tan IIA显著抑制了二氧化硅诱导的上皮-间质转化（EMT）和转化生长因子- β 1 (tgf - β 1)/Smad信号通路，降低了二氧化硅诱导的氧化应激，激活了A549和人支气管上皮（HBE）细胞的核因子-红细胞2相关因子-2 （Nrf2）信号通路。此外，通过转染siRNA，我们证明Nrf2激活部分介导Tan IIA对二氧化硅暴露诱导的EMT和tgf - β 1/Smad信号通路激活的抑制作用，从而介导Tan IIA对二氧化硅诱导的肺纤维化的抗纤维化作用。在我们的研究中，Tan IIA已被确定为一种可能的抗氧化和抗纤维化药物。
Silicosis is an occupational pulmonary fibrosis that is caused by inhalation of silica (SiO2), and there are no effective drugs to treat this disease. Tanshinone IIA (Tan IIA), a natural product, has been reported to possess antioxidant and anti-fibrotic properties in various diseases. The purpose of the current study was to examine Tan IIA's protective effects against silica-induced pulmonary fibrosis and to explore the underlying mechanisms. We found that in vivo treatment with Tan IIA significantly relieved silica-induced lung fibrosis in a silicosis rat model by histological and immunohistochemical analyses. Further, in vitro mechanistic investigations, mainly using western blot and immunofluorescence analyses, revealed that Tan IIA administration markedly inhibited the silica-induced epithelial-mesenchymal transition (EMT) and transforming growth factor-beta 1 (TGF-beta 1)/Smad signaling pathway and also reduced silica-induced oxidative stress and activated the nuclear factor erythroid 2-related factor-2 (Nrf2) signaling pathway in A549 and human bronchial epithelial (HBE) cells. Furthermore, through transfection with siRNA, we demonstrate that Nrf2 activation partially mediates the suppression effects of Tan IIA on EMT and TGF-beta 1/Smad signaling pathway activation induced by silica exposure, thus mediating the anti-fibrotic effects of Tan IIA against silica-induced pulmonary fibrosis. In our study, Tan IIA has been identified as a possible anti-oxidative and anti-fibrotic drug for silicosis.