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1,25-Dihydroxyvitamin D Enhances Alveolar Fluid Clearance by Upregulating the Expression of Epithelial Sodium
Hongguang Nie1, Yong Cui2, Sihui Wu1
1Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, Liaoning 110122, China.
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.
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