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

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.