1,25-Dihydroxyvitamin D Enhances Alveolar Fluid Clearance by Upregulating the Expression of Epithelial Sodium Channels

J Pharm Sci. 2016 Jan;105(1):333-8. doi: 10.1016/j.xphs.2015.11.022. Epub 2016 Jan 13.

Abstract

Vitamin D is implicated in the pathogenesis of asthma, acute lung injury, and other respiratory diseases. 1,25-Dihydroxyvitamin D (1,25(OH)2D3), the hormonal form of vitamin D, has been shown to reduce vascular permeability and ameliorate lung edema. Therefore, we speculate that 1,25(OH)2D3 may regulate alveolar Na(+) transport via targeting epithelial Na(+) channels (ENaC), a crucial pathway for alveolar fluid clearance. In vivo total alveolar fluid clearance was 39.4 ± 3.8% in 1,25(OH)2D3-treated mice, significantly greater than vehicle-treated controls (24.7 ± 1.9 %, n = 10, p < 0.05). 1,25(OH)2D3 increased amiloride-sensitive short-circuit currents in H441 monolayers, and whole-cell patch-clamp data confirmed that ENaC currents in single H441 cell were enhanced in 1,25(OH)2D3-treated cells. Western blot showed that the expression of α-ENaC was significantly elevated in 1,25(OH)2D3-treated mouse lungs and 1,25(OH)2D3-treated H441 cells. These observations suggest that vitamin D augments transalveolar fluid clearance, and vitamin D therapy may potentially be used to ameliorate pulmonary edema.

Keywords: alveolar fluid clearance; cell culture; epithelial; membrane transport; monolayer; patch-clamp technique; pulmonary; short-circuit current.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitriol / pharmacology*
  • Capillary Permeability / drug effects
  • Cell Line
  • Epithelial Sodium Channel Agonists / pharmacology*
  • Epithelial Sodium Channels / biosynthesis*
  • Epithelial Sodium Channels / genetics
  • Extravascular Lung Water / metabolism
  • Lung / cytology
  • Lung / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Patch-Clamp Techniques
  • Pulmonary Alveoli / drug effects*
  • Pulmonary Alveoli / metabolism*
  • Pulmonary Edema / drug therapy
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics

Substances

  • Epithelial Sodium Channel Agonists
  • Epithelial Sodium Channels
  • RNA, Messenger
  • Calcitriol