Am. J. Respir. Crit. Care Med., Volume 161, Number 4, April 2000, 1322-1331

Epithelial Na⁺ Channel (ENaC) Expression in the Developing Normal and Abnormal Human Perinatal Lung

DAVID E. SMITH, GAIL OTULAKOWSKI, HERMAN YEGER, MARTIN POST, ERNST CUTZ, and HUGH M. O'BRODOVICH

Lung Biology Programme of the Hospital for Sick Children and Departments of Paediatrics, Physiology, and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

Impaired lung epithelial Na⁺ channel (ENaC) activity at the time of birth results in respiratory distress. To investigate potential mechanisms, the ontogeny and cellular distribution of the ENaC subunit mRNA expression was studied in normal, immature, and abnormal (hypoplastic) human fetal lungs using nonradioisotopic in situ hybridization. Surprisingly, ENaC expression was detected at the embryonic stage of normal lung development (4 to 5 wk gestation) when expression was localized to the fetal lung bud epithelium. By late gestation, ENaC was expressed in the conductive and respiratory airway epithelium, serous cells, and the distal lung unit in an alveolar type II (ATII) epitheliumlike distribution. Significant ENaC expression was found in newborn lung diseases associated with respiratory distress. One explanation is that ENaC mRNA is constitutively expressed, and that activity is regulated, at least in part, at the post-transcriptional level. Alternative explanations are that the expression of the  or ENaC subunits may be impaired in certain newborn lung diseases or that alternate Na⁺ permeant channels or transporters are important to lung liquid absorption in humans at birth.

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