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Allyl isothiocyanate may reverse the expression of MRP1 in COPD rats via the Notch1 signaling pathway

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In the present study, the roles of AITC in up-regulating the MRP1 expression and its relationship with the activation of the Notch1 signaling pathway were investigated by combining the in vivo and in vitro experiments. AITC was administered to the COPD model rats and normal rats to explore the association between Notch1 and MRP1. The human bronchial epithelial cells were treated with DAPT, the Notch1 signaling pathway inhibitor, to verify the effect of Notch1 on the expression of AITC-induced MRP1. Compared with the control group, the expressions of Notch1, Hes1 (the target gene of Notch1) and MRP1 in the lung tissue of the COPD model group were significantly inhibited. In contrast to the COPD model group, the expressions of MRP1, Hes1 and Notch1 dramatically up-regulated following the treatment with Low/High doses of AITC. The expression of MRP1 in the 16 HBE cells was down-regulated by the inhibition of Notch in a DAPT concentration-dependent manner. Additionally, the AITC-induced up-regulation of the MRP1 expression was markedly impaired following the inhibition of Notch1. The above results indicated that the pulmonary function and the expression of MRP1 in COPD rats could be improved by AITC, which was partly dependent on the Notch1 signaling pathway. Therefore, targeting the Notch signaling pathway may present as an effective therapeutic strategy for COPD treatment.

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The present study was supported by the National Natural Science Foundation of China (Grant Nos. 81473536 and 81001592).

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Correspondence to Zegeng Li or Dianlei Wang.

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Wu, J., Wang, X., Yao, Z. et al. Allyl isothiocyanate may reverse the expression of MRP1 in COPD rats via the Notch1 signaling pathway. Arch. Pharm. Res. 42, 1000–1011 (2019).

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