Effect of fiber length on carbon nanotube-induced fibrogenesis.

Effect of fiber length on carbon nanotube-induced fibrogenesis.
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DOI:
10.3390/ijms15057444
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发表时间:
2014-04-29
影响因子:
5.6
通讯作者:
Rojanasakul Y
Rojanasakul Y
中科院分区:
生物学2区
文献类型:
--
作者:
Manke A;Luanpitpong S;Dong C;Wang L;He X;Battelli L;Derk R;Stueckle TA;Porter DW;Sager T;Gou H;Dinu CZ;Wu N;Mercer RR;Rojanasakul Y

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鉴于其极小的尺寸和轻的重量,碳纳米管(CNT)可以容易地被人类肺部吸入,导致肺部疾病,特别是纤维化的发病率增加。虽然CNT的纤维化潜力已得到充分证实,但关于CNT的物理化学属性对潜在纤维化结果的贡献缺乏共识。我们设计了一种实验验证的体外成纤维细胞培养模型,旨在研究纤维长度对单壁碳纳米管(SWCNT)诱导的肺纤维化的影响。通过氧化应激产生、胶原蛋白表达和转化生长因子-β(TGF-β)产生作为潜在的纤维化生物标志物来评估对短和长SWCNT的纤维化反应。长SWCNT在活性氧(ROS)响应、胶原蛋白产生和TGF-β释放方面比短SWCNT显著更有效。此外,我们在长度依赖性体外纤维化反应方面的发现通过体内肺纤维化结果得到了验证,从而支持体外模型的预测价值。我们的研究结果还证实了ROS在SWCNT诱导的胶原表达和TGF-β活化中的关键作用,表明了SWCNT诱导的纤维化的潜在机制。总之,我们的研究为纤维长度在SWCNT诱导的肺纤维化中的作用提供了新的证据,并提供了一种快速的基于细胞的纳米材料纤维化检测方法,能够预测体内肺纤维化反应。
Given their extremely small size and light weight, carbon nanotubes (CNTs) can be readily inhaled by human lungs resulting in increased rates of pulmonary disorders, particularly fibrosis. Although the fibrogenic potential of CNTs is well established, there is a lack of consensus regarding the contribution of physicochemical attributes of CNTs on the underlying fibrotic outcome. We designed an experimentally validated in vitro fibroblast culture model aimed at investigating the effect of fiber length on single-walled CNT (SWCNT)-induced pulmonary fibrosis. The fibrogenic response to short and long SWCNTs was assessed via oxidative stress generation, collagen expression and transforming growth factor-beta (TGF-β) production as potential fibrosis biomarkers. Long SWCNTs were significantly more potent than short SWCNTs in terms of reactive oxygen species (ROS) response, collagen production and TGF-β release. Furthermore, our finding on the length-dependent in vitro fibrogenic response was validated by the in vivo lung fibrosis outcome, thus supporting the predictive value of the in vitro model. Our results also demonstrated the key role of ROS in SWCNT-induced collagen expression and TGF-β activation, indicating the potential mechanisms of length-dependent SWCNT-induced fibrosis. Together, our study provides new evidence for the role of fiber length in SWCNT-induced lung fibrosis and offers a rapid cell-based assay for fibrogenicity testing of nanomaterials with the ability to predict pulmonary fibrogenic response in vivo.
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