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

ABSTRACT

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 α-, β-, and γ-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.

KEYWORDS:

• acute lung injury
• alveolar fluid clearance
• amiloride-insensitive sodium channel
• concentration-sensitive sodium channel
• pulmonary edema

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Funding

This work was supported by MEXT KAKENHI (grant number 20790183) and a research grant from Kindai University (RK18-31).