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Respiratory Research

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Open Access 01-12-2019 | Acute Respiratory Distress-Syndrome | Research

Lipoxin A₄ ameliorates lipopolysaccharide-induced lung injury through stimulating epithelial proliferation, reducing epithelial cell apoptosis and inhibits epithelial–mesenchymal transition

Authors: Jing-xiang Yang, Ming Li, Xin-ou Chen, Qing-quan Lian, Qian Wang, Fang Gao, Sheng-wei Jin, Sheng-xing Zheng

Published in: Respiratory Research | Issue 1/2019

Abstract

Background

Acute respiratory distress syndrome (ARDS) is characterized by alveolar epithelial disruption. Lipoxins (LXs), as so-called “braking signals” of inflammation, are the first mediators identified to have dual anti-inflammatory and inflammatory pro-resolving properties.

Methods

In vivo, lipoxinA₄ was administrated intraperitoneally with 1 μg/per mouse after intra-tracheal LPS administration (10 mg/kg). Apoptosis, proliferation and epithelial–mesenchymal transition of AT II cells were measured by immunofluorescence. In vitro, primary human alveolar type II cells were used to model the effects of lipoxin A₄ upon proliferation, apoptosis and epithelial–mesenchymal transition.

Results

In vivo, lipoxin A₄ markedly promoted alveolar epithelial type II cells (AT II cells) proliferation, inhibited AT II cells apoptosis, reduced cleaved caspase-3 expression and epithelial–mesenchymal transition, with the outcome of attenuated LPS-induced lung injury. In vitro, lipoxin A₄ increased primary human alveolar epithelial type II cells (AT II cells) proliferation and reduced LPS induced AT II cells apoptosis. LipoxinA₄ also inhibited epithelial mesenchymal transition in response to TGF-β₁, which was lipoxin receptor dependent. In addition, Smad3 inhibitor (Sis3) and PI3K inhibitor (LY294002) treatment abolished the inhibitory effects of lipoxinA₄ on the epithelial mesenchymal transition of primary human AT II cells. Lipoxin A₄ significantly downregulated the expressions of p-AKT and p-Smad stimulated by TGF-β₁ in primary human AT II cells.

Conclusion

LipoxinA₄ attenuates lung injury via stimulating epithelial cell proliferation, reducing epithelial cell apoptosis and inhibits epithelial–mesenchymal transition.

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Title: Lipoxin A4 ameliorates lipopolysaccharide-induced lung injury through stimulating epithelial proliferation, reducing epithelial cell apoptosis and inhibits epithelial–mesenchymal transition
Authors: Jing-xiang Yang
Ming Li
Xin-ou Chen
Qing-quan Lian
Qian Wang
Fang Gao
Sheng-wei Jin
Sheng-xing Zheng
Publication date: 01-12-2019
Publisher: BioMed Central
Keyword: Acute Respiratory Distress-Syndrome
Published in: Respiratory Research / Issue 1/2019
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/s12931-019-1158-z

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