Inhibitory effect of lipoxin A4 on epithelial-mesenchymal transition of alveolar epithelial type Ⅱ cell and its potential mechanism
Objective To investigate the effect of lipoxin A4(LXA4)on the epithelial-mesenchymal transition(EMT)of alveolar epithelial type Ⅱ cell(AT Ⅱ)and its potential mechanisms.Methods A549 cells were divided into five groups:control group,transforming growth factor β1(TGF-β1)group,empty vector+TGF-β1 group,pcDNA3.1-Nrf2+TGF-β1 group and LXA4+TGF-β1 group.A549 cells were treated with 5 ng/mL TGF-β1 for 48 h in TGF-β1 group.In empty vector+TGF-β1 group and pcDNA3.1-Nrf2+TGF-β1 group,A549 cells were respectively transfected with empty vector and pcDNA3.1-Nrf2,and then treated with 5 ng/mL TGF-β1 for 48 h.In LXA4+TGF-β1 group,A549 cells were pretreated with 100 nmol/L LXA4 for 6 h,and then stimulated with 5 ng/mL TGF-β1 for 48 h.The morphological changes of A549 cells were observed under light microscope,the expression levels of E-cadherin and α-smooth muscle actin(α-SMA)were examined by immunofluorescence assay and immunoblotting,and the protein level of nuclear factor erythroid 2-related factor 2(Nrf2)was measured by immunoblotting.Results Compared with control group,a part of A549 cells showed a morphological change from a pebble-like shape to an irregular elongated shape in TGF-β1 group.Compared with control group,the expression of E-cadherin was downregulated(P＜0.05),α-SMA was upregulated(P＜0.01),and the protein level of Nrf2 was decreased in TGF-β1 group(P＜0.05).Compared with TGF-β1 group,the E-cadherin expression was upregulated(P＜0.05)andα-SMA expression was decreased in pcDNA3.1-Nrf2+TGF-β1 group(P＜0.01),and the expression levels of E-cadherin and Nrf2 were increased and α-SMA expression was decreased in LXA4+TGF-β1 group(P＜0.05).Conclusion LXA4 can inhibit the EMT of A549 cells by upregulating Nrf2.
pulmonary fibrosisalveolar epithelial type Ⅱ cellepithelial-mesenchymal transitionlipoxin A4Nrf2
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