title: 1,25-Dihydroxyvitamin D Enhances Alveolar Fluid Clearance by Upregulating the Expression of Epithelial Sodium Channels.
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.
authors: Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, Liaoning 110122, China. Electronic address: hgnie@mail.cmu.edu.cn.
authors: Hongguang
authors: H
authors: Nie
authors: Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110122, China.
authors: Yong
authors: Y
authors: Cui
authors: Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, Liaoning 110122, China.
authors: Sihui
authors: S
authors: Wu
authors: Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, Liaoning 110122, China.
authors: Yan
authors: Y
authors: Ding
authors: Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, Liaoning 110122, China; Department of Medicine, Division of Biological Sciences, University of Chicago, Chicago, Illinois 60637.
authors: Yanchun
authors: Y
authors: Li
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002460:Cell Line; D062708:Epithelial Sodium Channel Agonists / Q000494:pharmacology*; D053503:Epithelial Sodium Channels / Q000096:biosynthesis* / Q000235:genetics; D015633:Extravascular Lung Water / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018408:Patch-Clamp Techniques; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism*; D011654:Pulmonary Edema / Q000188:drug therapy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D062708:Epithelial Sodium Channel Agonists; D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D002117:Calcitriol
keywords: alveolar fluid clearance; cell culture; epithelial; membrane transport; monolayer; patch-clamp technique; pulmonary; short-circuit current