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Maresin1 stimulates alveolar fluid clearance through the alveolar epithelial sodium channel Na,K-ATPase via the ALX/PI3K/Nedd4-2 pathway.

Zhang, Jun-Li and Zhuo, Xiao-Jun and Lin, Jing and Luo, Ling-Chun and Ying, Wei-Yang and Xie, Xiang and Zhang, Hua-Wei and Yang, Jing-Xiang and Li, Dan and Gao Smith, Fang and Jin, Sheng-Wei (2017) Maresin1 stimulates alveolar fluid clearance through the alveolar epithelial sodium channel Na,K-ATPase via the ALX/PI3K/Nedd4-2 pathway. Laboratory investigation; a journal of technical methods and pathology. ISSN 1530-0307. This article is available to all HEFT staff and students via ASK HEFT Discovery tool http://tinyurl.com/z795c8c using their HEFT Athens Login.

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Official URL: http://www.nature.com/labinvest/journal/vaop/ncurr...

Abstract

Maresin1 (MaR1) is a new docosahexaenoic acid-derived pro-resolving agent that promotes the resolution of inflammation. In this study, we sought to investigate the effect and underlining mechanisms of MaR1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. MaR1 was injected intravenously or administered by instillation (200 ng/kg) 8 h after LPS (14 mg/kg) administration and AFC was measured in live rats. In primary rat alveolar type II epithelial cells, MaR1 (100 nM) was added to the culture medium with lipopolysaccharide for 6 h. MaR1 markedly stimulated AFC in LPS-induced lung injury, with the outcome of decreased pulmonary edema and lung injury. In addition, rat lung tissue protein was isolated after intervention, and we found MaR1 improved epithelial sodium channel (ENaC), Na,K-adenosine triphosphatase (ATPase) protein expression and Na,K-ATPase activity. MaR1 down-regulated Nedd4-2 protein expression though PI3k/Akt but not though PI3k/SGK1 pathway in vivo. In primary rat alveolar type II epithelial cells stimulated with LPS, MaR1-upregulated ENaC and Na,K-ATPase protein abundance in the plasma membrane. Finally, the lipoxin A4 Receptor inhibitor (BOC-2) and PI3K inhibitor (LY294002) not only blocked MaR1's effects on cAMP/cGMP, the expression of phosphorylated Akt and Nedd4-2, but also inhibited the effect of MaR1 on AFC in vivo. In conclusion, MaR1 stimulates AFC through a mechanism partly dependent on alveolar epithelial ENaC and Na,K-ATPase activation via the ALX/PI3K/Nedd4-2 signaling pathway. Our findings reveal a novel mechanism for pulmonary edema fluid reabsorption and MaR1 may provide a new therapy for the resolution of ALI/ARDS.Laboratory Investigation advance online publication, 20 February 2017; doi:10.1038/labinvest.2016.150.

Item Type: Article
Additional Information: This article is available to all HEFT staff and students via ASK HEFT Discovery tool http://tinyurl.com/z795c8c using their HEFT Athens Login.
Subjects: WO Surgery > WO500 Anaesthesia
Divisions: Clinical Support > Anaesthetics
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Depositing User: Mr Philip O'Reilly
Date Deposited: 24 Mar 2017 13:51
Last Modified: 24 Mar 2017 13:51
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1282

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