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Tenascin-C Participates Pulmonary Injury Induced by Paraquat Through Regulating TLR4 and TGF-β Signaling Pathways

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Abstract—

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.

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Funding

This work was supported by National Natural Science Foundation of China (Nos. 81571882 and 81772053).

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Authors and Affiliations

  1. Emergency Department, First Hospital of China Medical University, Shenyang, China

    Di Zhang, Zhi Liu, Qianqian Liu, Honghai Lan, Jinjin Peng, Xiaowei Liu & Wei Liu

  2. Emergency Department, First Hospital of China Medical University, Shenyang, China

    Wei Liu

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Contributions

Liu Wei designed the study, Zhang Di, Liu Zhi, Liu Qianqian, Lan Honghai, Peng Jin jin, and Liu Xiaowei performed experiments, Liu Wei and Zhang Di analyzed data. The manuscript was drafted and edited by Zhang Di, Liu Zhi, and Liu Wei. All authors approved the submitted work.

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Correspondence to Wei Liu.

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Zhang, D., Liu, Z., Liu, Q. et al. Tenascin-C Participates Pulmonary Injury Induced by Paraquat Through Regulating TLR4 and TGF-β Signaling Pathways. Inflammation 45, 222–233 (2022). https://doi.org/10.1007/s10753-021-01540-w

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