This study was conducted to investigate the role of Tenascin-C (TNC) in paraquat (PQ)-induced lung injury in vivo and in vitro and explore its related mechanism during this process. Six- to eight-week-old male C57BL/6 mice were injected with 30 mg/kg PQ by intraperitoneal injection and sacrificed on 2 days, 7 days, 14 days, and 28 days after PQ administration. In vivo, we detected the expression of TNC at all time points of lung tissues in mice by reverse transcription-quantitative-polymerase chain reaction, western blotting, and immunohistochemistry. Expression of TLR4, NF-κB p65, TGF-β1, and α-SMA in lung tissues have also been tested. In vitro, siRNA was used to knock down TNC expression in A549 cells and TLR4, NF-κB p65, and TGF-β1 expressions were examined after PQ exposure. TNC expression increased in both lung tissues of mice model and A549 cells after PQ administration. In vivo, TNC mostly located at the extracellular matrix of thickened alveolar septum, especially at sites of injury, together with the increasing of TLR4, NF-κB p65, TGF-β1, and α-SMA. In vitro, PQ exposure also increased the expressions of TLR4, NF-κB p65, and TGF-β1 in A549 cells, but knocking down TNC gene expression obviously down-regulated the expressions of TLR4, NF-κB p65, NF-κB Pp65, and TGF-β1. The results of this study demonstrate, for the first time, that TNC participates in the development of lung injury induced by PQ poisoning. The role of TNC in this process is closely related to TLR4 and TGF-β signaling pathways.

本研究旨在探讨生腱蛋白-C (TNC)在体内 和体外在百草枯 (PQ) 诱导的肺损伤中的作用，并探讨其在此过程中的相关机制。6-8周龄雄性C57BL/6小鼠腹腔注射30mg/kg百草枯，在百草枯给药后2天、7天、14天和28天处死。在体内，我们通过逆转录-定量-聚合酶链反应、蛋白质印迹和免疫组织化学检测小鼠肺组织各时间点TNC的表达。还测试了 TLR4、NF-κB p65、TGF-β1 和 α-SMA 在肺组织中的表达。体外, siRNA 用于敲低 A549 细胞中的 TNC 表达，并在 PQ 暴露后检查 TLR4、NF-κB p65 和 TGF-β1 的表达。PQ 给药后小鼠模型和 A549 细胞的肺组织中 TNC 表达增加。在体内，TNC主要位于增厚的肺泡间隔细胞外基质，尤其是损伤部位，同时TLR4、NF-κB p65、TGF-β1和α-SMA的增多。体外, PQ 暴露也增加了 A549 细胞中 TLR4、NF-κB p65 和 TGF-β1 的表达, 但敲低 TNC 基因表达明显下调 TLR4、NF-κB p65、NF-κB Pp65 和 TGF 的表达-β1。这项研究的结果首次表明，TNC 参与了百草枯中毒引起的肺损伤的发展。TNC在这一过程中的作用与TLR4和TGF-β信号通路密切相关。