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

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-kappa B p65, TGF-beta 1, and alpha-SMA in lung tissues have also been tested. In vitro, siRNA was used to knock down TNC expression in A549 cells and TLR4, NF-kappa B p65, and TGF-beta 1 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-kappa B p65, TGF-beta 1, and alpha-SMA. In vitro, PQ exposure also increased the expressions of TLR4, NF-kappa B p65, and TGF-beta 1 in A549 cells, but knocking down TNC gene expression obviously down-regulated the expressions of TLR4, NF-kappa B p65, NF-kappa B Pp65, and TGF-beta 1. 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-beta signaling pathways.

Automated summary

This study demonstrates that TNC plays a significant role in paraquat-induced lung injury, and its function in this process is closely related to the TLR4 and TGF-beta signaling pathways.