beta-Elemene suppresses the proliferation of human airway granulation fibroblasts via attenuation of TGF-beta/Smad signaling pathway
beta-Elemene suppresses the proliferation of human airway granulation fibroblasts via attenuation of TGF-beta/Smad signaling pathway
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β-榄香烯通过减弱 TGF-β/Smad 信号通路抑制人气道颗粒成纤维细胞的增殖
DOI：
10.1002/jcb.28915
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发表时间：
2019
影响因子：
4
通讯作者：
Chen Xiao Yang
中科院分区：
文献类型：
--
作者：
Xue Cheng;Lin Xiao Ping;Zhang Jia Min;Zeng Yi Ming;Chen Xiao Yang
研究背景气道肉芽组织增生是良性气道狭窄易复发的原因。本课题组前期的研究证明，中药β-榄香烯能抑制体外培养的成纤维细胞的增殖，从而降低乳腺癌的复发率。我们首先将正常人气道成纤维细胞和人气道肉芽成纤维细胞与不同浓度的β-榄香烯培养相同时间或相同剂量的β-榄香烯培养不同时间，以探索药物与这些细胞之间的剂量/时间-效应关系。然后利用基因芯片技术筛选出药物影响人气道肉芽成纤维细胞的最重要途径。结果β-榄香烯对人气道肉芽成纤维细胞增殖有抑制作用，且呈剂量依赖性，对正常人气道成纤维细胞无影响。影响转化生长因子β（TGF-β）/Smad通路的表达可能是其作用的关键机制。该途径在人气道肉芽成纤维细胞中被激活，β-榄香烯以剂量依赖性方式抑制该途径。结论抑制TGF-β/Smad通路可能是β-榄香烯抑制人气道肉芽成纤维细胞增殖的重要机制。该通路可能是治疗良性气道狭窄的一个有希望的靶点。
BackgroundBenign airway stenosis is easily to recur as a result of hyperplastic airway granulation tissues. Our previous study proved that a Chinese drug, β‐elemene, could inhibit the proliferation of fibroblasts cultured from these tissues, which could decrease the recurrence rate of this disease.MethodsTo find out the mechanism for this effect, we first cultured normal human airway fibroblasts and human airway granulation fibroblasts with different concentrations of β‐elemene for the same time or the same dose of β‐elemene for different times to explore the dose/time‐effect relationship between the drug and these cells. Then we used gene microarray to screen out the most important pathway by which the drug influenced human airway granulation fibroblasts. At last, we assessed the condition of this pathway in human airway granulation fibroblasts and verified the effect of this drug on this pathway.Resultsβ‐Elemene inhibited the proliferation of human airway granulation fibroblasts in a dose but no time‐dependent manner and did not affect normal human airway fibroblasts. Affecting the expression of transforming growth factor β (TGF‐β)/Smad pathway may be the key mechanism for this effect. This pathway was activated in human airway granulation fibroblasts and β‐elemene inhibited it in a dose‐dependent manner. This effect was similar to the pathway inhibitor, SB431542, and exogenous TGF‐β could attenuate this effect.ConclusionThese results indicated that suppressing TGF‐β/Smad pathway was possibly the key mechanism by which β‐elemene inhibits the proliferation of human airway granulation fibroblasts. This pathway may be a promising target to treat benign airway stenosis.