Low expression of human epithelial sodium channel in airway epithelium of preterm infants with respiratory distress.
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 alpha-ENaC knockout mice died postnatally as a result of respiratory insufficiency. In animals, the expression of alpha-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 alpha-, beta-, and gamma-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 alpha-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 (alpha-hENaC: 5.38 +/- 2.01 [amol/fmol cytokeratin 18] vs 9.13 +/- 2.26; beta-hENaC: 2.44 +/- 1.43 vs 4.25 +/- 1.10; gamma-hENaC: 2.43 +/- 0.11 vs 6.81 +/- 3.24). Each of the 4 preterm infants who were treated with dexamethasone at approximately 1 month of age showed an increase in expression of alpha-hENaC and beta-hENaC subunit normalized to cytokeratin 18.


CONCLUSIONS
All 3 subunits of the hENaC are low in preterm relative to full-term infants. alpha-hENaC mRNA in respiratory epithelium is increased by therapeutic doses of glucocorticosteroid. Low expression of alpha-hENaC in human respiratory epithelium may play a role in the pathogenesis of respiratory distress in preterm infants.
Helve
Otto
O
Department of Neonatology, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland. otto.helve@hus.fi
Pitkänen
Olli M
OM
Andersson
Sture
S
O'Brodovich
Hugh
H
Kirjavainen
Turkka
T
Otulakowski
Gail
G
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D053503:Epithelial Sodium Channels; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D053503:Epithelial Sodium Channels; D005938:Glucocorticoids; D012333:RNA, Messenger; D015222:Sodium Channels; D003907:Dexamethasone