Expression of alpha-, beta-, and gamma-hENaC mRNA in the human nasal, bronchial, and distal lung epithelium.

Abstract

The amount of fluid covering the epithelium of the airways and alveolar space is modulated by active transport of Na+ from the lumen through the apical membrane Na+ permeant ion channels towards the interstitial space. We have measured the subunit expression of the amiloride-sensitive human Na+ channel (hENaC) by concomitant assessment of alpha-, beta-, and gamma-hENaC mRNA in the nasal, bronchial, and peripheral lung epithelia of adult patients undergoing lobectomy secondary to lung cancer. The study employed quantitative competitive reverse-transcriptase-polymerase chain reaction and qualitative in situ hybridization techniques. The hENaC mRNA content of each sample was normalized to the amount of epithelial cell-specific cytokeratin 18 (CK18) mRNA. Nasal epithelium contained significantly more (p < 0.05) alpha-hENaC mRNA (18 +/- 5 SD amol/fmol CK18), than bronchus (8 +/- 2 SD amol/fmol) and peripheral lung (9 +/- 2 SD amol/fmol). The ratio of gamma-hENaC/alpha-hENaC mRNA concentration was lowest in the nasal area, and it increased significantly towards the distal lung regions. The change in beta-hENaC mRNA was less profound. In situ hybridization studies of bronchial and peripheral lung sections selectively revealed expression of alpha-hENaC mRNA in superficial epithelium and submucosal glands of large airways, in bronchiolar epithelium, and in alveolar cells. We conclude that the relative expression of the hENaC subunit genes changes from the proximal to distal regions of the human respiratory tract.