Low Expression of Human Epithelial Sodium Channel in Airway Epithelium of Preterm Infants With Respiratory Distress
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* Departments of Neonatology
Cardiology, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland
Departments of Paediatrics and Physiology, University of Toronto, Toronto, Ontario, Canada
|| Programme in Lung Biology Research, Research Institute of the Hospital for Sick Children, Toronto, Ontario, Canada
Objective. Active ion transport is critical to postnatal clearance of lung fluid. The importance of epithelial sodium channel (ENaC) in this clearance has been demonstrated in animal studies in which 
-ENaC knockout mice died postnatally as a result of respiratory insufficiency. In animals, the expression of -ENaC in respiratory epithelium is dependent on gestational age, but when assessed by in situ hybridization in the human (h), the mRNA is present from the earliest stages of pulmonary development. Therefore, the purpose of the present investigation was to quantify mRNA of the -, ß-, and 
-hENaC subunits of newborn preterm infants with respiratory distress and compare the gene expression data against those detected in healthy term infants. In addition, the effect of systemic dexamethasone therapy on the 3 hENaC subunits was studied in 4 preterm infants who received prolonged assisted ventilation.
Methods. The expression of subunits of hENaC was determined in samples taken from nasal respiratory epithelium of 7 healthy term infants (gestation age: 39.3 ± 0.9 weeks [mean ± standard deviation) and 5 preterm infants (gestational age: 27.2 ± 0.9 weeks) with respiratory distress syndrome within 5 hours of birth. Betamethasone had been given to all mothers of preterm infants. In 4 additional preterm infants who still required assisted ventilation at 43 ± 6 days postnatal age, the expression of -hENaC was determined in samples taken before and during treatment with dexamethasone.
Results. Preterm infants with respiratory distress syndrome had low expression of all hENaC subunits relative to healthy term infants (-hENaC: 5.38 ± 2.01 [amol/fmol cytokeratin 18] vs 9.13 ± 2.26; ß-hENaC: 2.44 ± 1.43 vs 4.25 ± 1.10; -hENaC: 2.43 ± 0.11 vs 6.81 ± 3.24). Each of the 4 preterm infants who were treated with dexamethasone at 
1 month of age showed an increase in expression of -hENaC and ß-hENaC subunit normalized to cytokeratin 18.
Conclusion. All 3 subunits of the hENaC are low in preterm relative to full-term infants. -hENaC mRNA in respiratory epithelium is increased by therapeutic doses of glucocorticosteroid. Low expression of -hENaC in human respiratory epithelium may play a role in the pathogenesis of respiratory distress in preterm infants.
Key Words: epithelium • glucocorticoid • ion transport • lung liquid • respiratory distress syndrome
Abbreviations: ENaC, epithelial sodium channel • PD, potential difference • RDS, respiratory distress syndrome • hENaC, human epithelial sodium channel • QRT-PCR, quantitative reverse transcriptase–polymerase chain reaction • CK, cytokeratin
Received for publication Jan 17, 2003; Accepted Jul 14, 2003.
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