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

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 fi brosis(PF).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 signifi cantly increased at diff erent 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 signifi cantly correlated with that of TGF-β1 and Smad2(P<0.05 or P<0.01),instead of Wnt2 andβ-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.