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

Abstract

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 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.

Dynamic Changes in Histological and Morphometric Indicators of the Lungs in Sexually Immature Rats During Simulation of Partial Tracheal Stenosis

“…Раніше було встановлено, що виникнення фіб-розу пояснюється активацією фібропроліферативних процесів, кількісним збільшенням фіброцитів і фібробластів, накопиченням колагену, інших компонентів у екстрацелюлярному матриксі. Ці зміни супроводжуються розвитком ремоделюючих процесів у тканині легень [14]. Цей процес стосується стромальних елементів, у тканині легень, та характеризується збільшенням клітинної щільності [15].…”

The Mechanism and Effect of Autophagy, Apoptosis, and Pyroptosis on the Progression of Silicosis

“…Meanwhile, MCPIP1-siRNA reversed silica-induced autophagy and apoptosis of macrophages [ 31 , 32 ]. Like MCPIP1, zinc finger CCCH-type containing 4 protein (ZC3H4) greatly encouraged the autophagy level, further affecting epithelial-mesenchymal transition (EMT) in endothelial cells [ 33 , 34 , 35 ]. Concretely, ZC3H4 can be activated in multiple ways: (1) the competitive combination of circZC3H4 and miR-212 [ 36 ]; (2) the transcription of ZC3H4 mRNA (which may be caused by phosphorylation of Ets-like protein-1 (Elk-1)) [ 37 ].…”