In:
Shock, Ovid Technologies (Wolters Kluwer Health), Vol. 57, No. 4 ( 2022-04), p. 565-575
Abstract:
Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by increased permeability of the alveolar-capillary barrier and impaired alveolar fluid clearance. Resolvin E1 (RvE1) is a specialized pro-resolving mediator derived endogenously from omega-3-polyunsaturated fatty acids. RvE1 (10 μg/kg i.v.) was injected to rats 6 h post-lipopolysaccharide (LPS) (14 mg/kg) induction. After another 3 h, alveolar fluid clearance was measured in live rats (n = 8–9). The primary Type II alveolar epithelial cell was isolated and treated by LPS (1 μg/mL) with or without RvE1 (250 nM). The expression of epithelial sodium channel (ENaC), Na + /K + -ATPase (NKA), AKT, serum- and glucocorticoid-induced kinase 1 (SGK1), and Nedd4-2 were detected. RvE1 improved survival rate (30% vs. 70%, P = 0.048), increased the clearance of alveolar fluid (13.34% vs. 18.73%, P 〈 0.001), reduced lung wet-dry weight ratio (5.01 vs. 4.63, P 〈 0.001), mitigated lung injury scores (13.38 vs. 7.0, P 〈 0.05) and inflammation in LPS-induced ARDS in rats. RvE1 upregulated alveolar ENaC and NKA expression in vivo and in vitro . In addition, RvE1 significantly increased the expression of phosphorylated AKT, SGK1, and phosphorylated Nedd4-2 in LPS-stimulated primary alveolar type II cells. The effects of RvE1 were abrogated by blocking phosphatidylinositide3’-kinase (PI3K) and SGK1 with LY294002 and GSK650394, respectively. In summary, RvE1 upregulated ENaC and NKA expression by activating PI3K/AKT/SGK1 pathway to promote alveolar fluid clearance, suggesting that RvE1 may be a potentially effective drug for ARDS treatment.
Type of Medium:
Online Resource
ISSN:
1073-2322
,
1540-0514
DOI:
10.1097/SHK.0000000000001865
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2022
detail.hit.zdb_id:
2011863-6
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