1,25‐Dihydroxyvitamin D Enhances Alveolar Fluid Clearance by Up‐Regulating the Expression of Epithelial Sodium Channels

Abstract

PurposeVitamin D is implicated in the pathogenesis of asthma, acute lung injury and other respiratory diseases. 1,25‐ dihydroxyvitamin D (1,25‐VD), the hormonal form of vitamin D, has been shown to reduce vascular permeability and ameliorate lung edema (Chen SF, et al. 1995). Therefore, we speculate that 1,25‐VD may regulate alveolar Na+ transport via targeting epithelial Na+ channels (ENaC), a crucial pathway for alveolar fluid clearance (AFC).MethodsKM male mice (20~30g) were treated with active vitamin D analogue paricalcitol (daily i.p. injection) for 2 weeks before the in vivo AFC of these mice was measured. Western blotting was used to determine ENaC protein levels in mouse lungs and in human lung H441 epithelial cells treated with 1,25‐VD (20 nM). Whole cell patch‐clamp technique was used to measure ENaC activity in H441 cells.ResultsIn vivo total AFC was 31.9 ± 3.8% in paricalcitol‐treated mice, significantly greater than vehicle‐treated controls (19.7 ± 1.9%, n=10, P < 0.05). Amiloride‐sensitive AFC was increased approximately 50% by paricalcitol. Western blot showed that the expression of γ‐ENaC was significantly elevated in 1,25‐VD‐treated H441 cells and in paricalcitol‐treated mouse lungs. Amiloride‐sensitive Na+currents were greater (184%) in 1,25‐VD‐treated H441 cells compared to vehicle‐treated cells.ConclusionsThese observations suggest that vitamin D augments transalveolar fluid clearance, and vitamin D therapy may potentially be used to ameliorate pulmonary edema.This study was supported by the NSFC (30971181) to HG Nie, and NIH HL87017 to HL Ji.