Rapamycin protects against paraquat-induced pulmonary epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway.

Rapamycin protects against paraquat-induced pulmonary epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway.

Exp Ther Med. 2018 Mar;15(3):3045-3051

Authors: Vongphouttha C, Zhu J, Deng S, Tai W, Wu W, Li Z, Lei W, Wang Y, Dong Z, Zhang T

Abstract Paraquat (PQ) is a herbicide that is widely used in developing countries, and pulmonary fibrosisis one of the most typical features of PQ poisoning. The molecular mechanism underlying PQ toxicity is largely unknown, which makes it difficult to treat. In the present study, western blot analysis, reverse transcription-quantitative polymerase chain reaction and fluorescent immunostaining were used to analyze the effects of rapamycin on PQ-induced epithelial-mesenchymal transition (EMT) in A549 and MRC-5 cells. It was revealed that rapamycin significantly downregulated the mesenchymal cell marker, α-smooth muscle actin, and significantly upregulated the epithelial cell marker, E-cadherin, at mRNA and protein expression levels compared with the PQ group. Treatment with PQ significantly increased Wnt1, low-density lipoprotein receptor-related protein (LRP)5, LRP6 and β-catenin expression levels in A549 cells, while rapamycin significantly inhibited these effects of PQ. Activation of the Wnt signaling pathway using lithium chloride attenuated the inhibitory effects of rapamycin on PQ-induced EMT. In conclusion, rapamycin protects against PQ-induced pulmonary EMT via the Wnt/β-catenin signaling pathway.

PMID: 29599839 [PubMed]