Role of epithelial-to-mesenchymal transition in the pulmonary fibrosis induced by paraquat in rats

上皮间质转化在百草枯诱发大鼠肺纤维化中的作用

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作者:Jian-Hua Yi, Zhao-Cai Zhang, Mei-Bian Zhang, Xin He, Hao-Ran Lin, Hai-Wen Huang, Hai-Bin Dai, Yu-Wen Huang

Background

This study aims to explore the characteristics of the epithelial-to-mesenchymal transition (EMT) process and its underlying molecular mechanisms in the period of paraquat (PQ)-induced pulmonary fibrosis (PF).

Conclusions

EMT process plays a role in the PQ-induced PF, in which most PF and EMT markers have a peak phenomenon, and its underlying molecular mechanisms might be determined by further studies.

Methods

Picrosirius red staining and collagen volume fraction were utilized to evaluate the pathological changes of PQ-induced PF in rats. Immunohistochemistry, Western blot, and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were used to measure the protein and gene expression of EMT markers, EMT-associated transcription factors, and regulators of EMT-related pathways, respectively.

Results

The collagen deposition in the alveolar septum and increased PF markers were characteristics of pathological changes in PQ-induced PF, reached a peak on day 14 after PQ poisoning, and then decreased on day 21. The protein and gene expression of the fibrosis marker, EMT markers, transcription factors, and regulators of EMT-related signaling pathways significantly increased at different time points after PQ poisoning compared with corresponding controls (P<0.05), and most of them reached a peak on day 14, followed by a decrease on day 21. The gene expression of EMT markers was significantly correlated with PF markers, transcription factors, and regulators of EMT-related signaling pathways (P<0.05). The mRNA expression of transcription factors was significantly correlated with that of TGF-β1 and Smad2 (P<0.05 or P<0.01), instead of Wnt2 and β-catenin (P>0.05). Conclusions: EMT process plays a role in the PQ-induced PF, in which most PF and EMT markers have a peak phenomenon, and its underlying molecular mechanisms might be determined by further studies.

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