小白菊内酯通过 NF-κB/Snail 信号通路减轻博来霉素诱导的肺纤维化。
Parthenolide attenuated bleomycin-induced pulmonary fibrosis via the NF-κB/Snail signaling pathway.
机构信息
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China.
Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
出版信息
Respir Res. 2018 Jun 5;19(1):111. doi: 10.1186/s12931-018-0806-z.
BACKGROUND
Parthenolide (PTL) is a natural molecule isolated from Tanacetum parthenium that exhibits excellent anti-inflammatory and antitumor activities. Pulmonary fibrosis (PF), especially idiopathic pulmonary fibrosis (IPF), is a chronic lung disease that lacks a proven effective therapy. The present study evaluated the therapeutic effect of PTL on PF.
METHODS
Serum-starved primary lung fibroblasts and HFL1 cells were treated with different doses of PTL, and cell viability and the migration rate were measured. Western blot analysis and a dual-luciferase assay were used to analyze the epithelial-mesenchymal transition (EMT)-related transcription factors influenced by PTL treatment in A549 cells and primary lung epithelial cells. Mice with bleomycin (BLM)-induced pulmonary fibrosis were treated with different doses of intragastric PTL, and pathological changes were evaluated using Hematoxylin-eosin (H&E) staining and immunohistochemical analysis.
RESULTS
Our results demonstrated that PTL reduced the cell viability and migration rate of lung fibroblasts and inhibited the expression of EMT-related transcription factors in lung epithelial cells. In vivo studies demonstrated that PTL attenuated BLM-induced pulmonary fibrosis and improved the body weight and pathological changes of BLM-treated mice. We further demonstrated that PTL attenuated BLM-induced PF primarily via inhibition of the NF-κB/Snail signaling pathway.
CONCLUSION
These findings suggest that PTL inhibits EMT and attenuates BLM-induced PF via the NF-κB/Snail signaling pathway. PTL is a worthwhile candidate compound for pulmonary fibrosis therapy.
背景
小白菊内酯（PTL）是从蓬蒿属植物中分离得到的一种天然分子，具有优异的抗炎和抗肿瘤活性。肺纤维化（PF），特别是特发性肺纤维化（IPF），是一种慢性肺部疾病，缺乏有效的治疗方法。本研究评估了 PTL 对 PF 的治疗作用。
方法
用不同剂量的 PTL 处理血清饥饿的原代肺成纤维细胞和 HFL1 细胞，测量细胞活力和迁移率。Western blot 分析和双荧光素酶报告基因检测用于分析 PTL 处理后 A549 细胞和原代肺上皮细胞中上皮-间充质转化（EMT）相关转录因子的变化。用不同剂量的博来霉素（BLM）诱导肺纤维化的小鼠给予不同剂量的胃内 PTL 治疗，用苏木精-伊红（H&E）染色和免疫组化分析评估病理变化。
结果
我们的结果表明，PTL 降低了肺成纤维细胞的细胞活力和迁移率，并抑制了肺上皮细胞中 EMT 相关转录因子的表达。体内研究表明，PTL 减轻了 BLM 诱导的肺纤维化，并改善了 BLM 处理小鼠的体重和病理变化。我们进一步表明，PTL 通过抑制 NF-κB/Snail 信号通路减轻 BLM 诱导的 PF。
结论
这些发现表明，PTL 通过抑制 NF-κB/Snail 信号通路抑制 EMT 并减轻 BLM 诱导的 PF。PTL 是一种有前途的肺纤维化治疗候选化合物。
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