Gene expression of the concentration-sensitive sodium channel is suppressed in lipopolysaccharide-induced acute lung injury in mice

摘要

Purpose: The concentration-sensitive sodium channel (Na-C) is expressed in alveolar type II epithelial cells and pulmonary microvascular endothelial cells in mouse lungs. We recently reported that Na-C contributes to amiloride-insensitive sodium transport in mouse lungs (Respiratory Physiology & Neurobiology, 2016). However, details regarding its physiological role in the lung remain unknown. To examine whether Na-C is involved in alveolar fluid clearance during an acute lung injury (ALI), we analyzed the relationship between Na-C gene expression in the lung and the development of pulmonary edema in lipopolysaccharide (LPS)-induced ALI mice. Methods: LPS-induced ALI mice were prepared by the intratracheal administration of LPS. Bronchoalveolar lavage (BAL) neutrophils and lung water content (LWCs) were used as a marker of ALI and pulmonary edema, respectively. Na-C protein production in the lung was detected by immunoblotting and immunofluorescence. The gene expressions of Na-C and the epithelial sodium channel (ENaC) of LPS-induced ALI mice were examined by quantitative RT-PCR over a time course of 14 days. Results: The BAL neutrophil count increased until day 2 after LPS administration and had nearly recovered by day 6. LWCs in LPS-induced mice gradually increased until day 8 and had recovered by day 14. The expression of the Na-C protein in the lungs of LPS-induced mice dramatically decreased from day 2 to day 6, but recovered by day 8. The mRNA expression of Na-C decreased in the lung, as well as those for alpha-, beta-, and gamma-ENaC during ALI. Thus, Na-C expression is suppressed during the development stage of pulmonary edema and then recovers in the convalescent phase. Conclusion: Our results suggest that suppression of the gene expression of Na-C is involved in the development of pulmonary edema in ALI.