Paraquat induces acute respiratory distress syndrome by promoting the lung epithelial-mesenchymal transition

The acute respiratory distress syndrome (ARDS) is an important and common medical emergency. This study aimed to explore the molecular mechanism on how paraquat induced the occurrence of acute respiratory distress syndrome (ARDS). Rats were selected and treated with saline and paraquat for 5 and 21 days, respectively. Lung tissues were selected. Quantitative RT-PCR and western blotting were performed to screen the differentially expressed genes. Masson staining was performed to observe the morphological change of pulmonary fibrosis on lung tissues. Human lung epithelial cell lines HPAEpiC were treated with paraquat, and qRT-PCR was used to determine the changes of growth factor CTGF and TGF-β1, and markers for lung epithelial-mesenchymal transition (EMT) such as E-cadherin, N-cadherin, vimentin and MMP2. HPAEpiC cells were also treated with DMSO, scramble RNA + CTGF, siRNA against TGF-β1 + CTGF. The mRNA levels TGF-β1, Smad2, Samd3, E-cadherin, N-cadherin, vimentin and MMP2 were determined by qRT-PCR, and protein expression of Smad2 and Samd3 were determined by Western blotting. TNF-α, COL1A2, COL3A1, BMP-7, FASLG, TGF-β1 and CTGF were selected as differentially expressed genes. Masson staining showed collagenous fiber in lung tissues increased markedly when treating with paraquat. In HPAEpiC cells, paraquat increased the mRNA levels of CTGF, TGF-β1, E-cadherin, N-cadherin, vimentin and MMP2. CTGF increased the levels of TGF-β1, Smad2, Samd3, E-cadherin, N-cadherin, vimentin and MMP2. Paraquat can induce the occurrence of ARDS by activating TGF-β1/Smad2/3 pathway and promoting lung EMT.