肺
肺纤维化
纤维化
转化生长因子
脂多糖
血管紧张素转化酶2
化学
血管紧张素II
癌症研究
医学
内科学
受体
疾病
2019年冠状病毒病(COVID-19)
传染病(医学专业)
作者
Xingsheng Lin,Wensheng Lin,Yingfeng Zhuang,Fengying Gao
标识
DOI:10.1124/jpet.121.000907
摘要
In our previous studies, angiotensin-converting enzyme 2 (ACE2) was shown to alleviate the severity of acute lung injury, but its effects on the development of lung injury-caused lung fibrosis have not been studied.In the present study, the effects of ACE2 on lipopolysaccharide (LPS)-induced fibrosis in the lung were studied. The role of epithelial-mesenchymal transition (EMT) and that of the transforming growth factor β-1 (TGF-β1)/Smad2/Smad3 pathway in LPS-induced fibrosis in the lung were investigated.ACE2 expression in the mouse model of LPS-induced lung fibrosis was significantly increased. ACE2 activator diminazene aceturate (DIZE) significantly reduced pulmonary fibrosis, decreased alpha-smooth muscle actin expression, collagen I, hydroxyproline, and TGF-β1 in the lung. DIZE significantly decreased TGF-β1 expression and the activation of Smad2 and Smad3. ACE2 overexpression inhibited the LPS-induced EMT in MLE-12 cells (lung epithelial cells) and small interfering RNA treatment of ACE2 stimulated EMT. ACE2 overexpression also inhibited TGF-β1 expression and activation of Smad2 and Smad3 in MLE-12 cells. Finally, after MLE-12 cells were treated with both ACE2 and TGF-β1 plasmid, TGF-β1 plasmid significantly abolished the effect of ACE2 plasmid on the EMT in MLE-12 cells.Combined with the in vivo study, it was revealed that ACE2 can suppress the TGF-β1/Smad2/Smad3 pathway in lung type II epithelial cells, thus reversing their EMT and lung fibrosis. The present study provides basic research data for the application of ACE2 in lung injury-caused lung fibrosis treatment and clarifies the intervention mechanism of ACE2 in pulmonary fibrosis, which has potential value for clinical application.Angiotensin-converting enzyme 2 (ACE2) can inhibit the epithelial-mesenchymal transition (EMT) in lung type II epithelial cells and lung fibrosis. ACE2 can regulate the transforming growth factor β-1/Smad2/Smad3 pathway in lung type II epithelial cells, which may be the underlying mechanism of ACE2's effect on EMT and lung fibrosis.
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