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Increased ENaC-mediated liquid absorption across vitamin-D deficient human airway epithelia
Journal article   Peer reviewed

Increased ENaC-mediated liquid absorption across vitamin-D deficient human airway epithelia

Emma M Stapleton, Andrew L Thurman, Alejandro Antonio Pezzulo, Alejandro P Comellas and Ian M Thornell
American Journal of Physiology: Cell Physiology, Vol.326(2), pp.C540-C550
02/01/2024
DOI: 10.1152/ajpcell.00369.2023
PMCID: PMC11932534
PMID: 38145296

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Abstract

Vitamin D deficiency is a risk factor for exacerbation of obstructive airway disease, a hallmark of which is mucus dehydration and plugging. Calcitriol (the active form of vitamin D) deficiency in cultured human airway epithelia resulted in increased and mRNAs encoding subunits of ENaC and the Na-K pump compared to supplemented epithelia. These drive absorption of airway surface liquid. Consistently, calcitriol-deficient epithelia absorbed liquid faster than supplemented epithelia. Calcitriol-deficiency also increased amiloride-sensitive and without altering Na-K pump activity, indicating the changes in amiloride-sensitivity arose from ENaC. ENaC activity can be regulated by trafficking, proteases, and channel abundance. We found the effect was likely not induced by changes to endocytosis of ENaC given that calcitriol did not affect the half-lives of amiloride-sensitive and . Further, trypsin nominally increased produced by epithelia ± calcitriol, suggesting calcitriol did not affect proteolytic activation of ENaC. Consistent with mRNA and functional data, calcitriol deficiency resulted in increased γENaC protein. These data indicate that the vitamin D receptor response controls ENaC function and subsequent liquid absorption, providing insight into the relationship between vitamin D deficiency and respiratory disease.
 Ion transport ENaC Vitamin-D calcitriol airway

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